bluuebunny/crossref_metadata_2025 huggingface dataset:
Effect of nonsteroidal anti-inflammatory drugs on the microsomal monooxygenase system of rat liver
Authors: Bélanger P. M. , Atitsé-Gbeassor A.
Published: April 2011

The effect of acetylsalicylic acid, ibuprofen, indomethacin, ketoprofen, naproxen, phenylbutazone, and salicylic acid on the microsomal oxidative drug metabolism of rat liver was studied. Pretreatment of the rats with pharmacologic doses of acetylsalicylic acid, indomethacin, and ketoprofen decreased both the demethylase and hydroxylase activities of rat liver microsomes. These effects were paralleled by decreases in microsomal cytochrome P-450 content. The rate of the microsomal reactions was increased after pretreatment with ibuprofen and naproxen but only the former increased the concentration of cytochrome P-450. Phenylbutazone and salicylic acid had no in vivo effect on the hepatic monooxygenase. The addition of 1 mM of ibuprofen, indomethacin, ketoprofen, naproxen, and phenylbutazone to rat liver microsomes inhibit both the aminopyrine N-demethylase and p-nitro-anisole O-demethylase activities. The extent of the inhibition varied between 21 and 73% of the control incubation. Indomethacin, naproxen, and phenylbutazone also decreased the aniline hydroxylase activity to roughly 60% of the control value. Acetylsalicylic acid and salicylic acid had no in vitro effect on the microsomal monooxygenase. The nonsteroidal anti-inflammatory drugs produced a reverse type I binding spectrum with oxidized cytochrome P-450; indomethacin and phenylbutazone were the strongest ligands. There is no correlation between the effect of addition of nonsteroidal anti-inflammatory drugs to the hepatic microsomal homogenate and their in vivo effect on the monooxygenase activity.
Physiologic modulations of the systolic time intervals in the fetal lamb
Authors: Muylder Xavier De , Fouron Jean-Claude , Bard Harry , Lafond Josée S.
Published: April 2011

To examine the modulation of fetal systolic time intervals of the ovine fetus in relation to fetal maturation, heart rate, respiratory activity, and circadian rhythm, studies were carried out on 13 fetal–maternal sheep preparations. The data obtained showed that there was a significant correlation between the ejection time (ET) and the RR intervals of the electrocardiogram. The pre-ejection period (PEP) and PEP/ET increased in relation to the fetal maturation (38 ms and 0.25 at 120 days to 52 ms and 0.33 at 145 days of gestation, respectively). When the circadian rhythmicity was analyzed, a relative tachycardia was in evidence during the 21- to 03-h period but systolic time intervals remained unchanged. Except for some tachycardia and cardiac rhythm variability, respiratory activity also had no influence on the systolic time intervals.
Effect of disulfonic stilbene anion-channel blockers on the guinea-pig myocardium
Authors: Minocherhomjee Arda-E-Viraf M. , Roufogalis Basil D. , McNeill John H.
Published: April 2011

The role of anions in the maintenance of tension in electrically driven left atria isolated from guinea pigs has been examined. The disulfonic stilbene anion-channel blockers SITS (4-acetamido-4′-isothiocyanostilbene 2′-disulfonate) and DIDS (4,4′-diisothiocyano-2,2′-stilbene disulfonate) decreased the contractile force developed in a time- and concentration-dependent manner. As in the red cell anion channel, DIDS was more potent than SITS, but the maximal inhibition of tension produced by N-(4-azido-2-nitrophenyl)-2-aminoethyl sulfonate (NAP-taurine) was considerably lower than the near maximal inhibition produced by SITS and DIDS. The inhibition by SITS and DIDS was irreversible, suggesting a covalent interaction, and could not be overcome by increasing the calcium concentration or the frequency of stimulation. Consistent with a requirement for chloride anion, substitution of chloride and bicarbonate by the impermeant anion gluconate did not support contraction, while only partial tension was maintained with the lipophilic anions acetate and thiocyanate. Incubation of atria with 400 μM SITS blocked both 36Cl and 45Ca uptake to a similar extent, whereas the efflux of both these ions was not affected by incubation of the atria with SITS. The blockade by disulfonic stilbene anion-channel blockers of the contraction of the guinea pig myocardium may result from impairment of excitation–contraction coupling.
Prevention of diabetes-induced myocardial dysfunction in rats by methyl palmoxirate and triiodothyronine treatment
Authors: Tahiliani Arun G. , McNeill John H.
Published: April 2011

Diabetes results in myocardial functional alterations which are accompanied by a depression of biochemical parameters such as myosin ATPase and calcium uptake in the sarcoplasmic reticulum. Methyl palmoxirate, a fatty acid analog, is reported to decrease circulating glucose levels by inhibiting fatty acid metabolism, thus forcing carbohydrate utilization. In the present study, we attempted to prevent streptozotocin diabetes-induced myocardial alterations in the rat. Using the isolated working heart preparation, we observed a depression of myocardial function in rats 6 weeks after the induction of diabetes, which was characterized by the inability of these hearts to develop left ventricular pressures and rates of ventricular contraction and relaxation as well as control hearts at higher left atrial filling pressures. Methyl palmoxirate treatment (25 mg kg−1 day−1 po daily) was unable to control diabetes-induced changes in plasma glucose, triglycerides, insulin, and total lipids. Also, the functional depression seen in diabetic rat hearts was present despite the treatment. However, depression of calcium uptake and elevation of long chain acyl carnitines seen in sarcoplasmic reticulum (SR) prepared from diabetic rat hearts could be prevented by the treatment. As triiodothyronine (T3) treatment has been shown to normalize depression of cardiac myosin ATPase in diabetic rats, we repeated the study using a combination of T3 (30 μg kg−1 day−1 sc daily) and methyl palmoxirate. While diabetic rats treated with T3 alone did not show significant improvement of myocardial function when compared with untreated diabetics, the function of those treated with both T3 and methyl palmoxirate was not significantly different from that in control rat hearts. These results suggest that while the combination of T3 and methyl palmoxirate may have other effects which result in improved function, preventing the depression of myosin ATPase and the SR calcium uptake can account at least in part for the functional depression.
Regulation of lysophosphatidylcholine-metabolizing enzymes in isolated myocardial cells from rat heart
Authors: Severson David L. , Fletcher Thea
Published: April 2011

Enzymatic pathways involved in the metabolism of lysophosphatidylcholine were investigated in rat heart myocardial cells. Acyl CoA-dependent acyltransferase activity was localized in microsomes, and was much greater than lysophospholipase activity in either cytosolic or microsomal fractions. The cytosolic lysophospholipase was more sensitive to inhibition by palmitylcarnitine in comparison to free fatty acids. In contrast, free fatty acids (oleate and palmitate) produced a greater inhibition of the microsomal acyltransferase and lysophospholipase than did palmitylcarnitine. A reduction in the assay pH to 6.5 resulted in an increase in microsomal acyltransferase and cytosolic lysophospholipase activities, but brought about a marked reduction in the microsomal lysophospholipase activity. At pH 6.5, the percentage inhibition of the microsomal acyltransferase by palmitylcarnitine was reduced, whereas the inhibition by palmitic acid was enhanced. The inhibition of the microsomal lysophospholipase by both palmitylcarnitine and palmitic acid was reduced at pH 6.5. With respect to myocardial ischemia, the inhibition of microsomal acyltransferase by free fatty acids and the reduction in microsomal lysophospholipase activity due to acidosis may contribute to the elevation of cellular lysophosphoglycerides which are arrhythmogenic.
Adenosine receptors in smooth muscle: structure–activity studies and the question of adenylate cyclase involvement in control of relaxation
Authors: Baer H. P. , Vriend R.
Published: April 2011

Structure–activity studies with a number of adenosine derivatives and analogs, measuring their relaxant effects in a variety of smooth muscle systems, were conducted in the hope of obtaining indications of the possible involvement of adenylate cyclase in their mechanism of action. While it was confirmed that a C6 aminofunction is of importance for agonist activity, several compounds, in particular the relatively potent N6-hydroxylaminopurine ribonucleoside, were not antagonized by 8-p-sulfophenyltheophylline, indicating that some nucleosides cause smooth muscle relaxation by a mechanism other than adenosine receptor stimulation. Nucleosides not bearing a C6 aminofunction were essentially inactive in rabbit intestine but showed weak relaxant effects in bovine coronary artery; this may indicate a difference between the adenosine receptor systems in these tissues and the intracellular mechanisms of relaxation. Comparing the relative potencies of compounds such as adenosine, 2-chloroadenosine, 5′-(N-ethylcarboxamido)adenosine, and (−)N6-(R-phenylisopropyl)adenosine, which have been used widely to classify adenylate cyclase-coupled adenosine receptors, no uniform pattern became apparent among different smooth muscle systems used in this study and reported in the recent literature. Thus, we conclude that a classification of smooth muscle adenosine receptors according to criteria established for cyclase-coupled receptors may be inappropriate or misleading, particularly with respect to implications of adenylate cyclase involvement in the relaxant effects of adenosine and related nucleosides.
Sensitization of frog erythrocyte adenylate cyclase system by tumor-promoting phorbol diesters
Authors: Nambi Ponnal , Sibley David R. , Lefkowitz Robert J.
Published: April 2011

Preincubation of frog erythrocyte lysates with tumor-promoting phorbol diesters leads to an increase in adenylate cyclase activity. This stimulatory effect of phorbol diesters was specific. Incubation with 12-O-tctradecanoylphorbol 13-acetate led to increases in basal (38%) and isoproterenol- (40%), fluoride- (25%), and Mn-stimulated (68%) adenylate cyclase activities compared with control. The inactive phorbol diesters (4α-phorbol 12,13-didecanoate and β-phorbol) were ineffective in promoting increases in adenylate cyclase activity. The effect of active phorbol diesters was also observed on isolated frog erythrocyte membranes in the absence of cell supernatant, although to a much lesser extent than in the whole lysates. Addition of the cell supernatant or of purified protein kinase C to the membranes maximized the sensitization by the phorbol diesters. These data are consistent with the notion that some component(s) of the adenylate cyclase system is (are) phosphorylated by protein kinase C, resulting in an enhancement of enzyme activity.
The development of the small intestine
Authors: Thomson A. B. R. , Keelan M.
Published: April 2011

The remarkable degree of coordination between the development of various aspects of gastrointestinal function suggests that the process may be triggered by a single or a few central mechanisms, such as weaning and (or) hormones. Precocious development of enzyme and transport function can be induced by exogenous thyroxine and corticosteroids, while thyroidectomy and adrenalectomy abolish the normal pattern of postnatal development. These hormones may have a primary or a permissive role. Activation of the dormant hormonal mechanism could be controlled by a genetically coded biologic clock, such as chronologic age, or by a biological signal such as body size and oral intake. Generally speaking, shortly after birth, there are increases in the intestinal mucosal surface area, brush border membrane enzymes, and carrier-mediated transport. These adaptive changes occur as a result of the genetic endowment of the animal, but may be modified by environmental factors, particularly nutrient intake.
Changes in colonic myoelectric spiking activity during stimulation by bisacodyl
Authors: Schang J. C. , Hémond M. , Hébert M. , Pilote M.
Published: April 2011

The purpose of this study was to determine some relationships between colonic myoelectric spiking activity and intraluminal propulsion when colonic peristalsis was stimulated by bisacodyl. Myoelectric recordings were obtained in 12 subjects by means of a 50 cm long Silastic tube equipped with four bipolar electrodes fixed at 10-cm intervals. The tube was introduced into the left colon by flexible sigmoidoscopy and the electrodes were located at 50, 40, 30, and 20 cm from the anal verge. A small polyethylene catheter opening at the proximal end of the Silastic tube was used for introducing the laxative into the colon. One hour recording sessions were obtained before and after bisacodyl administration (5 mL of 0.4% solution). The control tracings showed that colonic spiking activity was made of rhythmic stationary bursts that ocurred at only one electrode site and of sporadic bursts that were either propagating over the whole colonic segment or nonpropagating. Administration of bisacodyl was followed by (i) complete suppression of the rhythmic stationary activity; (ii) a considerable increase in the sporadic spiking activity, propagating as well as nonpropagating; (iii) the occurrence of abdominal cramps and urgency to defecate, both associated with the propagating sporadic spike bursts. It is concluded that colonic propulsion induced by bisacodyl may be dependent upon the production of the sporadic bursts, particularly the propagating ones, while the rhythmic stationary bursts do not seem to play a significant role in colonic transit.
Effect of acetylcholine and secretin on medullary collecting duct function in the rat
Authors: Wilson D. R. , Honrath U. , Sonnenberg H.
Published: April 2011

Microcatheterization was used to study the effect of renal arterial infusion of acetylcholine or secretin on medullary collecting duct function in anaesthetized rats. Acetylcholine infusion was associated with natriuresis and increased sodium delivery to, and decreased reabsorption in, the collecting duct. No changes from control function were found with secretin. Renal blood flow was increased with acetylcholine (+82%, p < 0.001), but unchanged with secretin (+15%, nonsignificant). We conclude that acetylcholine natriuresis is due to inhibition of tubular reabsorption of sodium in the medullary collecting duct, as well as in upstream nephron segments. While the latter may be hemodynamically mediated, the former indicates a direct transport effect of the hormone in the terminal nephron segment.
Arachidonic acid induced coronary reactions and their inhibition by docosahexaenoic acid
Authors: Talesnik Jaime
Published: April 2011

The objective of the present study was to further investigate the influence exerted by docosahexaenoic acid (DHA) on the coronary reactions induced in isolated perfused hearts of rats and guinea pigs by bolus doses of arachidonic acid (AA). As in previous studies, we found that AA produced a coronary constriction followed by a longer lasting dilatation. The present data demonstrate that a 5-min infusion of DHA at 0.17–0.68 μM caused a concentration-dependent inhibition of the AA-induced constriction. The vasodilatation determined by AA was also depressed, but only after about 30 min of a sustained DHA infusion. The precursor of AA, linoleic acid (LA), was also infused for about 30 min, and like DHA it inhibited the coronary reactions induced by AA. LA is not converted into AA by the isolated heart, but like DHA, was probably incorporated into the cells of the coronary vascular compartment. It is known that LA, administered "in vivo" to mammals, is converted into AA and increases the production of eicosanoids, whereas DHA does not follow this metabolic pathway. The incorporation of these essential polyunsaturated fatty acids by the isolated perfused heart would inhibit the cyclooxygenase in the coronary vessel walls, interfering with the generation of vasomotor metabolites from AA. We postulate that the systemic administration of DHA, by inhibiting the synthesis of a constrictor metabolite, could be beneficial in reducing the damage due to microvascular constriction in myocardial ischaemia.
Reactivation processes of three inward current systems involved in the rising phase of the action potentials in embryonic chick hearts
Authors: Sada Hideaki , Sada Shigeko , Sperelakis Nicholas
Published: April 2011

In embryonic chick hearts during development, there are three inward current systems which are involved in the rising phases of the action potentials (APs): fast INa, slow ICa, and tetrodotoxin-insensitive slow INa. To assess reactivation processes for these three types of inward current channels (fast Na+, slow Ca2+, and slow Na+ channels), diastolic recovery of [Formula: see text] was examined in embryonic chick hearts using a paired-pulse protocol. In all cases, the diastolic recoveries were approximated by single exponential functions. The time constants of recovery [Formula: see text] and T90% (the diastolic interval which allows 90% recovery of [Formula: see text] of the premature AP) were, respectively, 53.1 ± 5.2 and 61.5 ± 8.6 ms for the Na+-dependent fast AP (n = 10), 376.9 ± 49.3 and 659.2 ± 113.1 ms for the Ca2+-dependent slow AP (n = 10), and 40.7 ± 5.3 and 45.6 ± 12.0 ms for the Na+-dependent slow AP (n = 10). In the presence of lidocaine, the recovery kinetics also appeared to be single exponentials for diastolic intervals up to 500 ms (fast APs) or 250 ms (slow APs). The reactivation processes for the Na+-dependent fast and slow channels were significantly slowed by 100 μM lidocaine. In addition, in the presence of 100 μM lidocaine, [Formula: see text] was depressed in a frequency-dependent manner; the higher the stimulation frequency, the greater the depression. Hence, the fast Na+ channels and the slow Na+ channels had the following similarities: rapid reactivation, reactivation slowed by lidocaine, and frequency-dependent depression in the presence of lidocaine.
Alterations in alpha1-adrenoceptor stimulation of isolated atria from experimental diabetic rats
Authors: Jackson Charles V. , McGrath Gail M. , McNeill John H.
Published: April 2011

This purpose of this investigation was to determine the influence of experimental diabetes (3 months) on the responsiveness of rat isolated atria to alpha1-adrenoceptor stimulation by phenylephrine. Diabetes was chemically induced with streptozotocin (65 mg/kg i.v.) in 42- to 43-day-old, nonfasted male Sprague–Dawley derived rats. Chronotropic (right atria) and inotropic (left atria) indices were recorded in response to alpha1-adrenoceptor stimulation by phenylephrine. These experiments were performed in the presence of beta-adrenoceptor antagonism (timolol). Isolated right atria from diabetic rats demonstrated a greater increase in heart rate in response to phenylephrine than did corresponding control atria. Left atria were supersensitive (decrease in EC50 values) and hyperresponsive to alpha1-adrenoceptor stimulation by phenylephrine when compared with stimulation of control left atria. Diabetic left atria in response to phenylephrine were observed to exchange more radioactive calcium (45Ca2+) than control left atria, whereas both diabetic and control left atria exchanged the same amount of 45Ca2+ during basal contractile conditions. Phenylephrine had no effect on 45Ca2+ efflux from either diabetic or control atria. These results indicate that 3 months of uncontrolled experimental diabetes in the rat produces an enhancement of alpha1-adrenoceptor activation of isolated atria, and that there is an alteration in Ca2+ mobilization which may contribute to the enhanced receptor activation.
Effects of insulin perfusion and altered glucose concentrations on heart function in 3-day and 6-week diabetic rats
Authors: Tahiliani Arun G. , McNeill John H.
Published: April 2011

Diabetes is known to result in depression of myocardial function, whereas hearts from insulin-treated diabetic rats exhibit functional characteristics similar to controls. In the present study, we have studied the effect of insulin perfusion on cardiac performance of 3-day and 6-week streptozotocin (STZ) diabetic rats. Three days of diabetes did not result in depressed cardiac performance when the hearts were isolated and perfused in the working heart mode. Increasing the concentration of glucose from 5 to 10 mM in the perfusion fluid did not alter the function in either control or in diabetic rat hearts. However, when regular insulin or glucagon-free insulin (Humulin®) (5 mU/mL) was included in the perfusion medium, the ventricular function of hearts from control rats was significantly enhanced, while diabetic myocardial function remained unaffected. When the study was repeated on hearts from 6-week diabetic animals, cardiac function of diabetic rats was significantly depressed as compared with controls. As in the 3-day study, contractility was not affected in either group by increasing glucose concentration in the perfusion medium. Again, inclusion of insulin in the medium enhanced cardiac contractility only in control hearts. These results suggest that diabetes results in a loss of myocardial sensitivity to insulin which seems to occur as early as 3 days after induction of diabetes with STZ. The study also demonstrates that the beneficial effects of in vivo insulin treatment on myocardial alterations induced by diabetes are not due to its direct myocardial effects.
Effects of temperature on the transport of nucleosides in guinea pig erythrocytes
Authors: Jarvis S. M. , Martin B. W.
Published: April 2011

The initial rate of [14C]uridine transport by guinea pig erythrocytes was investigated at different temperatures. At 37, 22, and 10 °C the concentration dependence of uridine zero-trans influx and equilibrium exchange influx was resolved into two components; (a) a saturable component which followed simple Michaelis-Menten kinetics and which was inhibited by nitrobenzylthioinosine, and (b) a linear component of low magnitude and insensitive to nitrobenzylthioinosine inhibition. The maximum velocity, Vmax, of zero-trans uridine influx for the saturable transport system was 70-fold higher at 37 than 10 °C (1.24, 0.20, and 0.018 mmol/L of cells per hour at 37, 22, and 10 °C, respectively). Similarly, the apparent affinity, Km, for zero-trans influx decreased as the temperature was lowered (0.27, 0.066, and 0.038 mM at 37, 22, and 10 °C, respectively). In contrast, uridine equilibrium exchange influx was less temperature dependent (Vmax, 2.80, 0.89, and 0.14 mmol/L of cells per hour; apparent Km 0.61,0.36, and 0.24 mM at 37, 22, and 10 °C, respectively). These results demonstrate that the mobility of the empty carrier is impaired to a greater extent than the mobility of the loaded carrier as temperature decreased. However, the kinetic constants for zero-trans uridine influx and efflux at 37 °C were similar, indicating that the nucleoside transporter exhibited directional symmetry at 37 °C. Arrhenius plots of the maximum velocity for equilibrium exchange and zero-trans uridine influx were discontinuous above 25 °C, but between 20 and 5 °C the plots were linear (Ea = 22 and 30 kcal/mol for equilibrium exchange and zero-trans influx, respectively).
Effect of insulin on gluconeogenesis and the metabolism of lactate in sheep
Authors: Brockman Ronald P. , Laarveld B.
Published: April 2011

Owing to the fermentative nature of their digestion, ruminant animals are highly dependent upon gluconeogenesis to meet their glucose needs. The role of hormones in regulating this process is not clear. The purpose of this study was to examine the effect of insulin on the utilization of lactate in glucose synthesis in sheep. The euglycemic model was used in sheep. [U-14C]Lactate and [6-3H]glucose were infused to monitor lactate and glucose fluxes. Hepatic metabolism was measured using radioisotopic and venoarterial concentration difference techniques. Insulin concentrations increased from basal concentrations of 16 ± 2 to 95 ± 9 μU/mL. Insulin reduced the net hepatic utilization of lactate (303 ± 43 vs. 120 ± 27 μmol/min), hepatic extraction efficiency of lactate (29 ± 4 vs. 9 ± 2%), hepatic output of glucose (338 ± 33 vs. 103 ± 21 μmol/min), and incorporation of lactate into glucose (90 ± 5 vs. 46 ± 8 μmol/min). Insulin at physiological levels can inhibit hepatic gluconeogenesis in ruminants.
Ovine fetal adrenal maturation at term and during fetal ACTH administration: evidence that the modulating effect of cortisol may involve cAMP
Authors: Challis J. R. G. , Lye S. J. , Welsh J.
Published: April 2011

Exogenous ACTH1–24 promotes adrenal maturation in fetal sheep, and this effect appears to be modulated in part by cortisol (Challis et al. 1985). We have examined whether similar changes in adrenal metabolism of progesterone occur with ACTH-induced labour as at spontaneous term and whether the site of cortisol modulation is on adrenal steroidogenesis or at the level of cAMP generation. Chronically catheterized fetal sheep were infused in utero for 100 h between days 127 and 131 of pregnancy with P-ACTH, P-ACTH + metopirone, P-ACTH + metopirone + cortisol, or saline. After 100 h the metabolism of [3H]progesterone was measured in adrenal homogenates. Similar incubations were performed with adrenal tissue from fetal sheep at day 130 of pregnancy and at spontaneous labour. In the treatment groups of sheep, cAMP output by dispersed adrenal cells in response to ACTH added in vitro was also determined. Similar qualitative patterns of [3H]progesterone metabolism were found in adrenal homogenates after in vivo ACTH or at term. At both times there was an increase in cortisol and in total 17α-hydroxycorticosteroid accumulation and also evidence for increased activity of 11β-hydroxylase enzyme. The formation of total 17α-hydroxycorticosteroids was not affected significantly by concurrent treatment in vivo with metopirone ± cortisol. The accumulation of cAMP in vitro was increased after in vivo ACTH, attenuated after ACTH + metopirone, but statistical significance over controls was restored after ACTH + metopirone + cortisol treatment. We conclude that ACTH-induced labour and spontaneous parturition in sheep is associated with qualitatively similar changes in progesterone metabolism by the fetal adrenal gland. These involve particularly an increase in 17α-hydroxylase and in 11β-hydroxylase activities. Our results do not suggest that the modulating effect of cortisol is exerted at 17α-hydroxylase but may be associated with processes leading to cAMP accumulation.
Differences between the effects of noradrenaline and the β-adrenoceptor agonist BRL 28410 in brown adipose tissue and hind limb of the anaesthetized rat
Authors: Thurlby Peter L. , Ellis Rodney D. M.
Published: April 2011

In mature (450–600 g) 21 °C-acclimated male rats, anaesthetized with urethane, blood flow (measured by the radioactive microsphere technique) to brown adipose tissue (BAT) was determined during the infusion of the β-adrenoceptor agonist BRL 28410 or noradrenaline bitartrate at doses chosen to give similar increases in whole body oxygen uptake. Blood flow to BAT during BRL 28410 infusion was only about one third of that found during noradrenaline infusion although increases in whole body thermogenesis were similar (55 and 77% for BRL 28410 and noradrenaline, respectively). This suggests that BAT may be less involved in the thermogenic response to BRL 28410 than to noradrenaline. In a separate experiment using slightly smaller rats (350–500 g) hind limb oxygen uptake was measured in situ using a venous bypass preparation. BRL 28410, at a dose having a maximum effect on whole body thermogenesis (53% increase), had no effect on oxygen delivery to the hind limb but significantly increased oxygen extraction by 33% (p < 0.001). In contrast, noradrenaline, also at a dose that maximally increased whole body thermogenesis, led to a 35% decrease in oxygen delivery to the hind limb and no change in oxygen extraction. For the thermogenic β-agonist BRL 28410 the hind limb, and presumably muscular tissue in general, may be contributing to thermogenesis.
Changes in electrical potential difference of rectal mucosa and of gallbladder bile constituents of dogs fed chenodeoxycholic acid
Authors: Shoenut J. Patrick
Published: April 2011

Eighteen dogs were studied for 54 days. Rectal mucosal electrical potential difference (PD), gallbladder bile acids, cholesterol, and phospholipids were measured. It was shown that feeding chenodeoxycholic acid (CDCA) for 24 days in dosages of 15, 30, and 60 mg/kg of body weight, all depressed PD equally but significantly (P < 0.05) in three groups of dogs compared with a control group. This depression was reversible 24 days after CDCA ingestion ceased in the two highest dosages. The low dose group was sacrificed after 24 days of CDCA feeding and the gallbladder bile was analyzed. CDCA and cholesterol were each significantly (P < 0.05) elevated over control values in the gallbladder bile of these dogs. Phospholipids were not significantly changed. The PD, a reflection of Na+–K+ ATPase activity, may be a useful indicator in maximizing dosages of CDCA in gallstone dissolution studies.
Potentiation of salivary fluid secretion in ixodid ticks: a new receptor system for γ-aminobutyric acid
Authors: Lindsay Paul J. , Kaufman W. Reuben
Published: April 2011

γ-Aminobutyric acid (GABA), having minimal intrinsic activity, potentiates dopamine-induced fluid secretion in salivary glands of female ixodid ticks. Because the effect of GABA was similar to that of spiperone, we tested whether these two drugs act at a common recognition site. Potentiation was not augmented when salivary glands were exposed to supramaximal concentrations of spiperone (1 μM) plus GABA (100 μM). (±)-Sulpiride (100 μM), a spiperone antagonist in this system, also blocked GABA-induced potentiation. Picrotoxin (100 μM) and (−)-bicuculline (100 μM), two GABA antagonists, blocked GABA-induced and spiperone-induced potentiation. Inhibition of GABA by picrotoxin and (−)-bicuculline was noncompetitive. Muscimol (an agonist at GABAA receptors) also potentiated dopamine-induced secretion. Baclofen (an agonist at GABAB receptors) did not elicit potentiation. We suggest that GABA may function as a neuromodulator for dopamine-induced fluid secretion in tick salivary glands.
Depressor effect of diabetes in the spontaneously hypertensive rat: associated changes in heart performance
Authors: Rodgers Robert L.
Published: April 2011

Effects of streptozotocin-induced diabetes (8 weeks) on the performance of perfused hearts from spontaneously hypertensive (SH) rats were compared with effects on normotensive Wistar–Kyoto (WK) and Sprague–Dawley (SD) rat hearts. Diabetes markedly decreased systolic arterial pressure (SAP) of SH rats in vivo but did not affect SAP of either of the normotensive strains. Diabetes also reduced heart size of SH and normotensive rats and reversed absolute left ventricular hypertrophy (wall-to-lumen ratios and left-to-right ventricular weight ratios) of SH rats. Heart perfusion at the end of the 8-week period revealed that diabetes (i) reduced hydraulic work at high pressure loads and efficiency of contraction (work/μ.LO2 consumed) of SH rat hearts but not of WK or SD hearts, and (ii) depressed left ventricular pulse pressure development (LVPP) and contractility (LV + dP/dt) of SH hearts more extensively than it reduced these variables in either of the normotensive control groups. Effects of diabetes which were similar in hypertensive and normotensive hearts were reductions in stroke work at high volume loads and depressions in LV−dP/dt. Attendant hypothyroidism probably contributed to the reductions in SAP, heart size, LVPP, LV+ and −dP/dt, and stroke work but not to the decreased efficiency or reversal of hypertrophy of SH rat hearts. Malnutrition of SH rats, like hypothyroidism, also decreased heart size without reversing hypertrophy but had no effect on SAP and only reduced LV−dP/dt. The results show that diabetes reversed hypertrophy and selectively reduced contraction efficiency, contractility, and LVPP of SH hearts, but otherwise the effects of diabetes in hypertensive and normotensive rat strains were similar to each other. The possible contribution of hypothyroidism to the observed effects of diabetes in SH rats remains to be clarified.
Membrane surface properties of lymphocytes of normal (DBA/2) and autoimmune (NZB/NZW)F1 mice: effects of L-canavanine and a proposed mechanism for diet-induced autoimmune disease
Authors: Prete Pamela E.
Published: April 2011

Partitioning cells in a dextran polyethylene glycol aqueous two-phase system (countercurrent distribution, CCD) is a sensitive method for learning about cell surface membrane properties and for subfractionating cell populations. In this study, we subjected lymphocytes from normal DBA/2 mice and autoimmune F1 New Zealand black/New Zealand white ((NZB/NZW)F1) mice to countercurrent distribution and found that T cells partition to the right and B cells partition to the left of the CCD curve. We found no difference between the CCD patterns of normal and autoimmune mice. When the murine lymphocytes were exposed to a cationic dietary amino acid (L-canavanine) in vitro, L-canavanine selectively affected the CCD pattern of autoimmune B cells, reflecting an alteration in surface membrane properties. We separated these lymphocytes with altered surface membrane properties by CCD. Impaired B-cell immune responses associated with L-canavanine were isolated to this lymphocyte fraction. This study provides the first evidence that alterations in the charged surface membrane properties are associated with abnormal (auto) immune response.
The influence of bile on the bioavailability of polynuclear aromatic hydrocarbons from the rat intestine
Authors: Rahman Anisur , Barrowman J. A. , Rahimtula A.
Published: April 2011

The mechanisms governing absorption of polynuclear aromatic hydrocarbons (PAHs) are important since these carcinogenic compounds occur as solutes in dietary lipids. These highly lipophilic compounds are well absorbed in the intestine. Bile salt micellar solubilization probably facilitates their transport across the unstirred water layer to the enterocytes. To study the role of bile in the intestinal absorption of PAHs, conscious rats with bile duct and duodenal catheters were given isotopically labelled 2,6-dimethylnaphthalene (DMN), phenanthrene, anthracene, 7,12-dimethylbenzanthracene (DMBA), and benzo[a]pyrene (BP); the recovery of radioactivity in bile and urine was measured. The PAHs were given intraduodenally in com oil with or without exogenous bile. Cumulative recovery of radiolabel in bile and urine over 24 h was used to assess the efficiency of absorption of the hydrocarbons with and without bile. The following values for absorption without bile (as percentage of absorption with bile) were obtained: DMN, 91.6%; phenanthrene, 96.7%; anthracene, 70.8%; DMBA, 43.4%; BP, 22.9%. The values for anthracene, DMBA, and BP were significantly less than 100% (P < 0.05); the values for DMN and phenanthrene were not significantly different from 100%. The dependence of the tricyclic compound anthracene (a structural isomer of phenanthrene) on bile for its absorption correlates with its lower water solubility. These results are consistent with the concept that the unstirred water layer presents a significant barrier to the absorption of this group of compounds and that micellar solubilization facilitates the uptake process.
On the role of luteinizing hormone-releasing hormone in the in vitro synthesis of hioactive human chorionic gonadotropin in human pregnancies
Authors: Belisle Serge , Bellabarba Diego , Gallo-Payet Nicole , Lehoux Jean-Guy , Guévin Jean-François
Published: April 2011

The dynamics of luteinizing hormone-releasing hormone (LHRH) induced human chorionic gonadotropin (hCG) production were studied in isolated placental cells from normal and anencephalic midterm and term gestations. A spontaneous release of immunoreactive hCG was first detected after 24–36 h of preparation in term control cells. The addition of LHRH at a concentration ranging from 10−9 to 10−6 M induced a threefold increase in this output of hCG. Placental cell responsiveness to LHRH varied according to the number of days of cell cultures, with maximal response on days 1 and 6. Placental cells from normal pregnancies incubated with 1 × 10−6 M LHRH showed a release of both immuno- and bio-assayable hCG, which was four- to six-fold higher at midgestation than at term (p < 0.001). In contrast, placental cells from pregnancies with anencephalic fetuses showed, at both stages of gestation, an hCG production that was comparable to that observed with normal term placental cells. We conclude that LHRH at a concentration appropriate for its placental receptor binding affinity induces a production of bioactive hCG in humans. Furthermore, our data suggest that anencephaly changes the placental response of hCG to LHRH stimulation.
Genetic effects in human skeletal muscle fiber type distribution and enzyme activities
Authors: Bouchard C. , Simoneau J. A. , Lortie G. , Boulay M. R. , Marcotte M. , Thibault M. C.
Published: April 2011

The purpose of the study was to estimate the genetic effect for skeletal muscle characteristics using pairs of nontwin brothers (n = 32), dizygotic (DZ) twins (n = 26), and monozygotic (MZ) twins (n = 35). They were submitted to a needle biopsy of the vastus lateralis for the determination of fiber type distribution (I, IIa, IIb) and the following enzymes were assayed for maximal activity: creatine kinase, hexokinase, phosphofructokinase (PFK), lactate dehydrogenase, malate dehydrogenase, 3-hydroxyacyl CoA dehydrogenase, and oxoglutarate dehydrogenase (OGDH). For the percentage of type I fibers, intraclass correlations were 0.33 (p < 0.05), 0.52 (p < 0.01), and 0.55 (p < 0.01) in brothers and DZ and MZ twins, respectively. MZ twins exhibited significant within-pair resemblance for all enzyme activities (0.30 ≤ r ≤ 0.68). In spite of these correlations, genetic analyses performed with the twin data alone indicated that there was no significant genetic effect for muscle fiber type I, IIa, and IIb distribution and fiber areas. Although there were significant correlations in MZ twins for all muscle enzyme activities, the often nonsignificant intraclass coefficients found in brothers and DZ twins suggest that variations in enzyme activities are highly related to common environmental conditions and nongenetic factors. However, genetic factors appear to be involved in the variation of regulatory enzymes of the glycolytic (PFK) and citric acid cycle (OGDH) pathways and in the variation of the oxidative to glycolytic activity ratio (PFK/OGDH ratio). Data show that these genetic effects reach only about 25–50% of the total phenotypic variation when data are adjusted for age and sex differences.
Chemical modification of calcium release from the sarcoplasmic reticulum of mechanically skinned skeletal bullfrog muscle fibers
Authors: Aoki Takako , Oba Toshiharu , Hotta Ken
Published: April 2011

Several types of reagents that react with amino acid side chains induced repetitive phasic contracture of skinned skeletal muscle from frogs. The presence of 10 mM procaine or 5 mM magnesium in the medium or disruption of the sarcoplasmic reticulum (SR) eliminated this contracture, indicating that the calcium-induced calcium-release mechanism of SR is involved in the contraction. Dithiothreitol inhibited the contracture induced by chloramine T, N-acetylimidazole, or p-chloromercuriphenylsulfonic acid (pCMPS) but not in the case of carbodiimide, phenylglyoxal, trinitrobenzenesulfonic acid, diethylpyrocarbonate (DEP), or N-chlorosuccinimide (NCS). Therefore, modification of groups other than the sulfhydryl ones seems to induce contractures under such conditions. The amplitude of the caffeine-induced contracture decreased after treatment with pCMPS, DEP, or NCS. NCS shifted the pCa–tension curve toward low pCa in the SR-disrupted fibers. This shift would explain the decrease in caffeine contracture. It is tentatively concluded that pCMPS and DEP release a large amount of calcium from SR.
Bile salt dependent bile flow in the rabbit: evidence for the importance of an amiloride inhibitabie pathway
Authors: Strasberg S. M. , Ilson R. G. , Bear C. E.
Published: April 2011

Bile salt dependent flow and electrolyte secretion in response to two bile salts were studied in awake rabbits. It was found that sodium glycodeoxycholate had a much greater choleretic and cholioneretic efficiency than sodium taurocholate. The effect of the bile salts on flow and electrolyte secretion was not linear across the range of bile salt secretion rates studied. When amiloride was administered significant decreases in choleretic and cholioneretic efficiencies occurred, but furosemide had no effect. It is concluded that bile salts stimulate electrolyte transport via amiloride inhibitable cellular processes, and that this electrolyte transport is in part responsible for bile salt dependent bile flow.
Effect of soman (pinacolyl methylphosphonofluoridate) on the blood levels of corticosterone and adrenocorticotropin in mice
Authors: Hudon Mark , Clement John G.
Published: April 2011

Mice were poisoned by an extremely toxic organophosphate anticholinesterase soman (pinacolyl methylphosphonofluoridate), 50 or 100 μg/kg at 1000, and the serum concentrations of corticosterone were determined fluorometrically at 3-h intervals for at least 24 h. The lower soman dose (50 μg/kg) produced a modest increase in serum corticosterone concentrations but by 24 h the levels were not significantly different from control. Following the higher soman dose (100 μg/kg) the serum corticosterone levels were elevated significantly (p < 0.05), for at least 27 h. However, ACTH concentrations were not elevated. It is possible that the elevated levels of corticosterone were due to a reduced metabolism and excretion of corticosterone resulting from the intense hypothermia, following soman poisoning which may change cardiac output and organ (liver and kidney) perfusion and not due to an enhanced release from the adrenal gland.
Bile salt related secretion of acid phosphatase in rat bile
Authors: Marinelli Raul A. , Luquita Marcelo G. , Rodríguez Garay Emilio A.
Published: April 2011

The biliary excretion of bile salts, lysosomal acid phosphatase, and total proteins were studied in rats under different experimental conditions: (i) during bile salt loss through a bile fistula and (ii) after loading with exogenous sodium taurocholate. The experimental models were suitable to demonstrate that variations in the excretion of bile salts were associated with those of acid phosphatase output. During bile salt depletion, acid phosphatase output showed a decrease parallel to that of bile salts. Following a single i.v. injection of sodium taurocholate and during its i.v. infusion, a rapid increase of acid phosphatase excretion in bile was seen. The patterns of enzyme outputs observed after administration of sodium taurocholate suggested a bulk discharge in bile of lysosomal contents. The profiles of protein output were similar to those of acid phosphatase suggesting an association between the secretory mechanism of these bile constituents. In contrast to sodium taurocholate, 4-methylumbelliferone, which also increases canalicular bile flow, did not produce changes in the excretory patterns of the bile components studied. Therefore, the results suggested a bile salt related secretion of acid phosphatase in the rat, which may involve protein secretion in bile.
Pressor effects of systemic administration of methionine and leucine enkephalin in the conscious rat
Authors: Thornhill J. A. , Ewen M. , Wilfong A. A. , Gregor L. , Saunders W. S.
Published: April 2011

Experiments were designed using conscious Spargue–Dawley rats to determine the blood pressure (BP) and heart rate (HR) responses to intravenous doses of (1) the adrenal catecholamines noradrenaline (NA) and adrenaline (A), (2) adrenal pentapeptides methionine enkephalin (ME) and leucine enkephaline (LE), (3) combination (i.v.) injections of both ME or LE with NA or A that modulate the hemodynamic responses when the adrenal catecholamines were given alone, and (4) the possible receptor mechanisms mediating the resultant BP and HR response to i.v. pentapeptide administration. NA (0.48 and 2.4 nmol) and A (0.3 and 1.5 nmol) given i.v. evoked potent, dose-related pressor responses associated with reflex bradycardia. ME and LE (1.6 – 48 nmol) elicited transient (10–20 s) increases in mean arterial pressure (MAP), which was associated either with no change in mean heart rate (MHR), such as ME, or with slight bradycardia (i.e., LE). Combining ME or LE (16 nmol) with NA (2.4 nmol) or A (0.3 or 1.5 nmol) did not change MAP and MHR from when these respective doses of NA or A were given alone. However, 16 nmol of ME or LE with a low dose of NA (0.48 nmol) increased the pressor response compared with NA (0.48 nmol) given alone. Other experiments whereby specific receptor blockers (naloxone, diprenorphine, atropine, propranolol, phentolamine or quanethidine) were given i.v. 5 min before subsequent i.v. administration of LE or ME (16 nmol) indicated that only phentolamine or quanethidine could completely suppress the pressor responses of LE and ME. Naloxone and diprenorphine pretreatment attenuated the pressor response of LE but did not affect the BP response to ME. The results suggest that i.v. LE or ME injections to conscious rats evoke an α-adrenergic receptor-mediated pressor response which is not associated with tachycardia and that is likely due to vasoconstriction of the peripheral vasculature.
Season and social environment influence the membrane integrity of ejaculated boar spermatozoa as assessed by ouabain sensitivity
Authors: Trudeau V. , Sanford L. M.
Published: April 2011

Eight adult Landrace boars were housed for 12 months in one of two social environments. Socially nonrestricted boars were penned near estrual females and socially restricted boars were penned behind solid walls to eliminate visual and physical contact with other pigs. All animals were subjected to natural changes in day length. The sensitivity of ejaculated spermatozoa to ouabain (in inhibitor of Na+–K+ ATPase) was determined on 4 consecutive weeks in November, March–April, and July–August. Semen was diluted in Tyrode's solution (pH 7.4) with and without 10−3 M ouabain. Duplicate samples of control and ouabain-treated spermatozoa were incubated at 37 °C for 4 h, and percent motile sperm, motility type, and motility index (combination of percent and type) were determined at hourly intervals. Oubain-induced decreases in most motility parameters varied with season (season × treatment, P < 0.05). At hour 4, induced decreases in percent motile sperm were more pronounced in November and July–August than in March–April for socially nonrestricted boars. Decreases in motility type were greater (P < 0.05) in November and July–August than in March–April for socially nonrestricted boars and were greater (P < 0.01) in November than in July–August for restricted boars. In March–April motility type decreased (P < 0.01) to a greater extent for socially restricted vs. nonrestricted boars. Similar season and social environment differences were observed for motility index values. Given the interrelationships between ouabain sensitivity, the functional integrity of sperm cells, and fertilizing capacity, season and social environment differences in ouabain-induced motility depression probably reflect qualitative changes in boar spermatozoa.