bluuebunny/crossref_metadata_2025 huggingface dataset:
Dopamine production by the isolated perfused rat kidney
Authors: Baines Andrew D. , Drangova Rosa
Published: April 2011

We used isolated perfused rat kidneys to examine dopamine (DA) production and its relation to renal function. Both innervated and chronically surgically denervated kidneys perfused with a solution containing neither albumin nor tyrosine, excreted 0.2 ± 0.1 ng DA∙min−1∙g wet weight−1 during the 10-min collection period between 30 and 40 min after starting perfusion. When perfused with 6.7% albumin, without tyrosine, innervated kidneys excreted 1.0 ± 0.06 ng DA∙min−1∙g−1 and denervated kidneys excreted 1.0 ± 0.07 DA∙min−1∙g−1. When 0.03 mM tyrosine was included in the albumin perfusate, innervated kidneys excreted 1.2 ± 0.1 ng DA∙min−1∙g−1 (p < 0.1). Under these conditions DA excretion continued for at least 100 min at which time it was 0.6 ng∙min−1∙g−1 and 86 ng/g kidney weight had been excreted. Denervated kidneys perfused with albumin + tyrosine excreted 0.9 ± 0.13 ng DA∙min−1∙g−1. Renal stores of free DA, conjugated DA, and dihydroxyphenylalanine (DOPA) could have provided at the most 30 ng/g of DA. Carbidopa inhibited DA excretion completely. DA excretion did not correlate with renal vascular resistance, inulin clearance, or fractional sodium excretion. In summary, nonneural tissue in isolated perfused kidneys produced DA at the same rate as denervated kidneys in vivo. Less than one-third of the DA produced by isolated kidneys could have come from intrarenal stores of DOPA, free DA, and conjugated DA; the rest was synthesized from unknown precursors. Circulating DOPA and tyrosine were not the DA precursors, but albumin was required to obtain production rates similar to those in vivo. Nonneuronal DA production did not influence renal hemodynamics, glomerular filtration rate (GFR), or sodium excretion.
Divergent pharmacological responses to two calmodulin inhibitors, chlorpromazine and W-7, in rat pancreatic acinar cells
Authors: Heisler Seymour , Fortin Anne
Published: April 2011

The possible role of calmodulin in exocytotic secretion is supported by the presence of this calcium-binding protein in secretory cells, and by the antisecretory effects in intact secretory cells of substances which can antagonize calmodulin-stimulated enzymes in broken cell preparations. In this study, two in vitro calmodulin antagonists, W-7 and chlorpromazine, were found to produce both similar and different pharmacological effects on the secretory process in rat exocrine pancreas. Both substances blocked amylase secretion in response to carbachol or cholecystokinin octapeptide, but only chlorpromazine inhibited the ability of carbachol to stimulate 45Ca efflux from isotope-preloaded cells. Only W-7 could inhibit the secretory response to vasoactive intestinal peptide (VIP); but both W-7 and chlorpromazine were equipotent partial antagonists of VIP-stimulated cyclic AMP synthesis. Chlorpromazine increased the secretory response to melittin but W-7 did not. The divergence in biological responsiveness to W-7 and chlorpromazine makes it difficult to extrapolate the in vitro effects of these agents to similar actions in intact cell systems.
The effects of an ASA-like hydroperoxide compound on adenosine diphosphate induced platelet aggregation
Authors: Killackey J. J. F. , Killackey B. A. , Cerskus I. , Philp R. B.
Published: April 2011

A hydroperoxide compound structurally related to acetylsalicylic acid, 3-hydroperoxy-3-methylphthalide, inhibits both the first and second phases of adenosine diphosphate induced, biphasic, human platelet aggregation. This occurs over the same concentration range (0.05–0.5 mM) that acetylsalicylic acid inhibits second phase aggregation and the release reaction only. The complete inhibition of adenosine diphosphate induced aggregation is a unique pharmacological property for an acetylsalicylic-acid-like compound.
The role of electrostatic interactions in modulating the local anaesthetic effects of amphipathic agents in frog skeletal muscle
Authors: Foulks James G. , Morishita Lillian
Published: April 2011

The local anaesthetic effect of cationic, anionic, and neutral alkyl amphipathic agents was similarly enhanced in an apparently nonspecific way by circumstances which modulate electrostatic interactions (acidity, modification of charged groups at the sarcolemmal surface by group-specific reagents, or changes in the calcium concentration), presumably as the result of secondary effects on the conformation of membrane proteins. However, the selective enhancement of the local anaesthetic effect of alkyl trimethylammonium compounds by perchlorate implies a more specific interaction which may influence the penetration of hydrophobic groups into the membrane interior.
The effects of vasoactive intestinal polypeptide on the motility of human and guinea pig gallbladder
Authors: Feeley Thomas M. , Clanachan Alexander S. , Scott Gerald W.
Published: April 2011

The effects of several preparations of vasoactive intestinal polypeptide (VIP) on the motility of strips of human and guinea pig gallbladder were investigated in vitro. VIP (10−12 to 10−6 M) had no measurable effects on the spontaneous activity, resting tone or cholecystokinin-octapeptide induced tone of human gallbladder strips. However, VIP (10−12 to 10−6 M) caused biphasic effects on the tone of guinea pig gallbladder strips. At low concentrations (10−12 to 10−10 M) contractions were observed that became smaller at higher concentrations (10−9 to 10−8 M). At still higher concentrations (10−7 to 10−6 M) relaxations were elicited. It appears that VIP is not as potent a relaxant of gallbladder muscle as first described. Human gallbladder tissue was totally unresponsive to the VIP preparations tested.
Effects of scorpion venom on structure and function of esophageal lower sphincter (LES) and body circular muscle (BCM) from opossum
Authors: Daniel E. E. , Posey-Daniel V.
Published: April 2011

In the lower esophageal sphincter (LES) and body circular muscle (BCM) from opossum, nerves appeared to innervate the interstitial cells of Cajal more closely than they innervated smooth muscle cells, and it was postulated that these cells might mediate nonadrenergic, noncholinergic (NANC) nerve effects. Tissues were treated with a toxin, selective for structures with Na channels, the venom of the scorpion, Leiurus quinquestriatus, to determine its morphological effects on nerves and other structures and its effect on responses of LES and BCM to NANC nerve stimulation by field stimulation with 0.5- and 5-ms pulses. Relaxations to 5-ms pulses are tetrodotoxin-insensitive and might result from the release of mediators from nerve terminals by a different, Na channel independent mechanism or from activation of a nonneural structure with a longer time constant than nerve. Scorpion venom relaxes the LES temporarily and, like tetrodotoxin, abolished responses of LES and BCM to 0.5-ms pulses of field stimulation, but not responses to 5-ms pulses of field stimulation. When responses to 0.5 ms of field stimulation were first inhibited, some nerve varicosities were damaged. Later nearly all were depicted markedly of synaptic vesicles. Venom did not structurally damage other cells. The venom effects to relax LES and to damage nerves were prevented by tetrodotoxin pretreatment, suggesting that venom released an inhibitory mediator and destroyed synaptic vesicles by acting on Na channels. The finding that interstitial cells of Cajal, which often had gap junction contacts to smooth muscle and close associations with nerves, were resistant to scorpion venom while the nerves that innervate them were not, is consistent with the hypothesis that interstitial cells are intercalated between the nerves and muscles and may mediate tetrodotoxin-insensitive responses to field stimulation.
Inhibition of the synthesis of hepatic cytochrome P-450 by the interferon-inducing agent poly rI.rC
Authors: Singh Gurmit , Renton Kenneth W.
Published: April 2011

The levels of cytochrome P-450, cytochrome b5, aminopyrine N-demethylase, and benzo[a]pyrene hydroxylase were depressed in hepatic microsomes following treatment of mice with the interferon inducer poly rI.rC. The decrease in the hepatic mixed function oxidase system was accompanied by an increase in the incorporation of amino acids into total microsomal protein. Fractionation of solubilized microsomes using a Sephacryl S-200 gel filtration column demonstrated that the increase in amino acid incorporation tended to be associated with proteins with molecular weights under 67 000. The fractions which contained cytochrome P-450 were further separated using a DEAE cellulose column. The amount of labelled amino acids associated with the cytochrome P-450 fractions was uniformly depressed in preparations from poly rI.rC treated animals compared with saline-treated controls. These results suggest that poly rI.rC causes a depression in the rate of synthesis of the apoprotein of cytochrome P-450 while increasing the incorporation of amino acids into other hepatic proteins. The decrease in apocytochrome P-450 synthesis explains the marked loss of drug biotransformation which occurs following induction of interferon.
Adrenal paraneurone contractile proteins and stimulus–secretion coupling
Authors: Trifaró J. M. , Kenigsberg R. L. , Côté A. , Lee R. W. H. , Hikita T.
Published: April 2011

Actin, myosin, and alpha-actinin have been isolated from adrenal chromaffin cells and characterized. Their physicochemical properties have been studied and their cell localization revealed by biochemical, immunocytochemical, and ultrastructural techniques. Alpha-actinin is a component of chromaffin granule membranes and some of the cell actin copurifies with these secretory granules. Myosin is not detected in the granules but is present mainly in the cytosol. Trifluoperazine, a calmodulin antagonist, blocks stimulation-induced hormone release from chromaffin cells at a step distal from Ca2+ entry. High affinity calmodulin binding sites have also been found in chromaffin granule membranes. Furthermore, microinjection of calmodulin antibodies into chromaffin cells blocks hormone output in response to stimulation. In view of the above findings, the possible roles of contractile proteins and calmodulin in chromaffin cell functions is discussed.
The adrenal paraneurone: tubulin organization
Authors: Bader M. F. , Bernier-Valentin F. , Rousset B. , Aunis D.
Published: April 2011

When chromaffin cells from the bovine adrenal medulla are maintained in culture, they develop neuritelike processes which end with growth-cone-like structures. Chromaffin granules were found to migrate from the cell body to the neurite endings. Thus, the intracellular transport of secretory granules, existing in vivo, seems to occur in an exaggerated way in the cultured cells. These cells offer an excellent model for studying the mechanism of transport, particularly the role of microtubules. By immunofluorescent staining, we observed that tubulin antibodies decorate a complex network visible along the neurites. Colchicine treatment induced the disappearance of this network followed by a return of granules in the cell body and a retraction of neurites. To test the presence of tubulin in the chromaffin granule membrane, we used two-dimensional gel electrophoresis and a radioimmunoassay. Our results indicate that tubulin is not a significant component of chromaffin granules. However, binding experiments show that granule membranes are able to bind tubulin through high affinity binding sites. These results show that microtubules appear involved in neurite formation and probably in granule transport. Tubulin is not an integral constituent of the granule membrane, but is present as a result of a reversible specific binding. This insertion of tubulin into the membrane might represent a step in the association between microtubules and secretory granules.
An acute and subacute neurotoxicity assessment of trichlorfon
Authors: Slott V. , Ecobichon D. J.
Published: April 2011

The toxicity of trichlorfon (O, O-dimethyl-2,2,2,-trichloro-1-hydroxyethylphosphonate, Dipterex®, Dylox®), reported to elicit delayed neurotoxicity in man and chickens, was studied by administering single subcutaneous doses of 100 or 300 mg/kg to adult White Leghorn hens. At 24 h posttreatment, the birds were observed for visible signs of neurotoxicity, were euthanized, and samples of blood plasma, brain, and spinal cord (cervical and thoracic regions) were obtained for quantification of cholinesterase and neurotoxic esterase (NTE) activities. In subacute studies, hens were dosed with trichlorfon (100 mg/kg) every 72 h for a total of six doses. Seventy-two hours after the final dose the hens were euthanized, the brains, spinal cords, and distal sciatic nerves were removed for enzymatic and (or) histological examination. Parallel acute and subacute studies were conducted using diisopropyl phosphorofluoridate (DFP), a known neurotoxic agent, at subcutaneous dosages of 1.0 mg/kg. In the acute studies, both DFP and trichlorfon markedly inhibited tissue cholinesterase activities but only DFP elicited a significant inhibition of NTE. In the subacute studies, DFP produced a characteristic central–peripheral distal axonopathy in the 18-day period of study which was confirmed by clinical and morphological evidence and by marked inhibition of neuronal NTE. Trichlorfon caused little or no obvious neurotoxicity, an observation that was supported by minimal morphological changes and impairment of walking ability and no inhibition of brain or spinal cord NTE.
The role of aortic chemoreceptors during acute anemia
Authors: Szlyk P. C. , King C. , Jennings D. B. , Cain S. M. , Chapler C. K.
Published: April 2011

The importance of aortic chemoreceptors in the circulatory and metabolic responses during acute anemia was studied in anesthetized dogs. Data were obtained from nine dogs in which the aortic chemoreceptors were surgically denervated prior to induction of anemia, and from seven sham-operated dogs. Cardiac output [Formula: see text], limb blood flow [Formula: see text], limb and whole body oxygen uptake [Formula: see text] were determined at normal hematocrit (Hct) and at 30 min of anemia (Hct = 13%) produced by isovolemic dextran-for-blood exchange. At 30 min of anemia, [Formula: see text] was increased from 91 to 186 mL∙kg−1∙min−1 (p < 0.01) and from 99 to 153 mL∙kg−1∙min−1 (p < 0.01) in the sham and denervated groups, respectively. The increase in [Formula: see text] during anemia was less (p < 0.05) in the aortic-denervated series. Limb flow was also increased during anemia in both groups (p < 0.01); the mean value of 89 mL∙kg−1∙min−1 in the denervated group was less than that of 130 mL∙kg−1∙min−1 observed in the sham animals (p < 0.05). Whole body [Formula: see text] decreased (p < 0.05) in the denervated group at 30 min of anemia; limb [Formula: see text] was maintained at the preanemic control value in both groups. The data indicate that during acute anemia the aortic chemoreceptors contribute to the increase in [Formula: see text].
Coronary venous pressure and flow: effects of vagal stimulation, aortic occlusion, and vasodilators
Authors: Klassen G. A. , Armour J. A.
Published: April 2011

Coronary venous pressure and coronary sinus flow in the canine heart were compared with intramyocardial, intraventricular, aortic, and coronary artery pressures. Stimulation of the thoracic vagus augmented coronary venous pressure, mean venous flow per systole, and coronary venous systolic resistance, but decreased the mean venous flow. Partial occlusion of the aorta augmented coronary venous pressure and coronary venous flow, while systolic coronary venous resistance remained unchanged. Adenosine increased peripheral and central coronary venous pressure and venous flow; it reduced peripheral coronary artery presure. Adenosine augmented flow per systole and reduced venous resistance more than the other interventions. Dipyridamole decreased left ventricular, aortic, and central coronary artery systolic pressures and systolic venous resistance. It increased the venous flow, mean flow per systole, and coronary venous pressure, even though intramyocardial pressure remained unchanged. Nitroglycerine elevated coronary venous pressure and flow, as well as venous flow per systole, even though it decreased left ventricular, aortic, and central coronary artery pressures. Nitroglycerine significantly decreased coronary venous resistance. It is concluded that coronary venous resistance may be an important resistive component to consider when the total coronary circulation is studied.
Naloxone-resistant effects of opioids on the twitch in frog skeletal muscle
Authors: Shetty Suraj S. , Frank George B.
Published: April 2011

Morphine and several other opioid agonists including the enkephalins caused a dual action on the twitch in the isolated, curarized, and electrically stimulated frog toe muscle: a potentiating action at low drug concentrations and a potentiation followed by an inhibitory action at higher concentrations. The twitch potentiation was found to be nonstereospecific and resistant to antagonism by naloxone. The inhibitory action too was naloxone-resistant and is probably due to a nonspecific local anesthetic effect of the opioids on the electric properties of the frog skeletal muscle fibre membrane.
Similar metabolic dependence of stimulated and unstimulated myocardial slow channels
Authors: Wahler Gordon M. , Sperelakis Nick
Published: April 2011

Cardiac slow action potentials (APs) induced by isoproterenol (which is thought to increase the number of slow channels in the open state at any instant in time) are metabolically dependent. This dependence may protect the myocardium during ischemia by reducing contractility (thus sparing ATP), while allowing conduction to be nearly normal. In this study, slow APs were elicited in fast Na+ channel inactivated cardiac cells by isoproterenol, or by tetraethylammonium (TEA) which increases the net inward current without increasing the number of open slow channels. In guinea pig papillary muscles paced at 0.5 Hz, 1 mM NaCN abolished both unstimulated (TEA-elicited) and stimulated (isoproterenol-elicited) slow APs with similar time courses: the mean abolition times being 9.5 ± 1.5 min for the unstimulated and 8.5 ± 2.0 min for the stimulated slow APs. Pretreatment of muscles with 55 mM glucose for 30 min prolonged (abolition time of 17.5 ± 4.5 min) or prevented (not abolished after 2 h) the NaCN abolition of slow APs. The duration of the normal fast APs was substantially reduced and the contractions ceased within 5–25 min of NaCN addition, whereas the upstroke velocity was only slightly depressed after 2 h. We conclude that unstimulated myocardial slow channels have a metabolic dependence similar to slow channels stimulated by inotropic agents.
Effect of quinidine on Na-dependent 45Ca transport in isolated adult cardiac cells
Authors: Désilets Michel , Horackova Magda
Published: April 2011

The effects of quinidine on Na+-dependent Ca2+ transport in adult rat isolated cardiac cells have been studied by measuring 45Ca2+ uptake and efflux at various external Na+ concentrations ([Na +]o). Quinidine (>50 μM) appreciably inhibited the Ca2+ uptake induced by lowering [Na+]o but had little effect on the Ca2+ efflux. The conclusion that the apparent inhibition of the Na+-dependent Ca2+ uptake was probably due to a general inhibition of the Ca2+ entry through cellular membrane and, at high concentrations, into the intracellular compartments rests on the observations that: (i) in non-steady-state conditions, the fraction of Ca2+ uptake inhibited by quinidine was independent of [Na+]o; (ii) lidocaine, which is known to have effects on membrane electrical activity and Na+ permeability similar to those of quinidine, did not affect the Ca2+ movements; and (iii) when incubated in low [Na+]o, quinidine (>0.2 mM) caused an irreversible contracture of a fraction of the myocyte population, even if about 50% of the Ca2+ uptake induced by lowering [Na+]o was inhibited. The results of this study therefore suggest that quinidine cannot be considered a specific inhibitor of the Na+–Ca2+ exchange in isolated rat cardiac myocytes and indicate the importance of quinidine's effects on intracellular Ca2+ regulation in cardiac muscle.
Reduced glutathione modulates the arachidonic acid induced coronary reactions
Authors: Talesnik Jaime , Tsoporis James N.
Published: April 2011

Coronary flow was recorded from spontaneously beating isolated perfused hearts of rats and guinea pigs. Arachidonic acid (AA), in single bolus doses, produced a fast short lasting coronary constriction followed by a slow developing but persisting vasodilation. These reactions (biphasic type) were characteristic of the guinea pig heart. In about 50% of the rat hearts the vasoconstrictor action predominated while the biphasic response was obtained in the rest of the experiments. Pretreatment of rats with aspirin prevented the responses to AA in the isolated heart. The administration of reduced glutathione (GSH) (about 1 mM to the rat or 0.5–0.75 mM to the guinea pig hearts) produced a marked development and (or) enhancement of the vasodilator action of AA. Repeated or single large doses of AA produced a change of pattern of responses from biphasic to constrictor type; the addition of GSH restored the vasodilator phase. Since GSH directs the endoperoxide metabolism towards the synthesis of prostaglandin E2 (PGE2), we postulate that the coronary dilatation of resistance vessels produced by AA would be due to a great extent to PGE2.
The function of motor nerves innervating slow tonic skeletal muscle in hens with delayed neuropathy induced by tri-o-tolyl phosphate
Authors: Durham H. D. , Ecobichon D. J.
Published: April 2011

The reduction of neurogenic posttetanic potentiation in the slow twitch, soleus muscle is an index of impaired motor nerve function in cats with organophosphate-induced neuropathy. We have applied the measurement of posttetanic potentiation to study the functional state of the slow, tonic, plantaris muscle and its motor innervation in adult White Leghorn hens with tri-o-tolyl phosphate (TOTP)-induced neuropathy. At suitable intervals following single oral doses of vehicle or TOTP (500 mg/kg), nerve conduction velocity and posttetanic potentiation were measured in anesthetized hens. Conduction in the sciatic nerve was not altered by TOTP. The plantaris muscle of birds treated with vehicle (peanut oil) either failed to contract or responded to nerve stimulation at 0.4 Hz with very small twitches. Following nerve stimulation at frequencies inducing tetanus (50–140 Hz), the muscles responded with large, slow twitches that gradually decayed in amplitude. The area under the curve formed by the amplitude of these twitches over time (posttetanic potentiation) was directly proportional to the frequency and duration of nerve stimulation. In hens at 1, 2, and 4 weeks following treatment with TOTP, the average amount of posttetanic potentiation was reduced concomitantly with the development of ataxia, paralysis, and pathological changes in the peripheral nerves. This difference between vehicle- and TOTP-treated hens was not significant, owing to large interbird variations. Since TOTP-treated hens showed greater disturbances in gait following moderate exercise, the fatigue of posttetanic potentiation with periodic neuronal stimulation was measured. In vehicle-treated birds, the posttetanic potentiation remained constant or increased slightly over the 2-h test period; whereas, in the TOTP-treated birds, there was a gradual and variable decrease in posttetanic potentiation, though this could not be correlated with the severity of the ataxia. In contrast with the cat, reduction of posttetanic potentiation in the hen was not a reliable index of the development of delayed neurotoxicity caused by TOTP.
The lipid content of the diabetic kidney of the rat
Authors: Lemieux Guy , Moulin Bruno , Davignon Jean , Huang Yung-Sheng
Published: April 2011

Rats were made diabetic by intravenous administration of streptozotocin, 100 mg/kg. Six groups of animals were studied: (1) normal; (2) animals given a supplement of 100% corn oil margarine; (3) insulin-treated normoglycemic diabetic; (4) hyperglycemic nonacidotic diabetic; (5) ketoacidotic diabetic; and (6) NH4Cl acidotic. The kidneys were removed from anesthetized animals. The renal cortex was separated from the medulla, freeze-clamped, and homogenized. Total lipids were extracted and measured gravimetrically. Lipid fractions were determined by thin-layer chromatography. Fatty acids of triacylglycerols and of phospholipids were analyzed by gas chromatography. Plasma triacylglycerols were elevated in hyperglycemic nonacidotic rats and more so in ketoacidotic animals. Total kidney lipids were 18% higher in nonacidotic hyperglycemic rats and 56% higher in ketoacidotic diabetic rats. This was due to accumulation of triacylglycerols while the phospholipid and cholesterol fractions did not change. Examination of long-chain fatty acids of kidney cortex triacylglycerols revealed that palmitate rose in a significant fashion while linoleate fell. This pattern was similar in all three groups of diabetic animals. The present data characterize the lipid content of the experimental rat diabetic kidney. They establish that the accumulation of lipids in the renal cortex during diabetes is related to triacyclgycerols and their palmitate content. Our study also provides a clear profile of plasma triacylglycerols during diabetes mellitus in the rat.
Thyroid hormones modulate ornithine decarboxylase in the immature rat cerebellum
Authors: Ruel Jean , Chénard Claire , Coulombe Pierre , Dussault Jean H.
Published: April 2011

In this study, we measured ornithine decarboxylase (ODC) activity as a potential parameter to evaluate the response of the developing rat brain to thyroid hormones. In cerebellum, neonatal hyperthyroidism (40 μg thyroxine/100 g body weight daily from birth) increased ODC activity at 2 and 5 days of age and then accelerated its developmental decline. Conversely, ODC activity was decreased in 2- and 5-day-old hypothyroid rats (propylthiouracil to the mother), but it was not significantly different from normal thereafter. No significant differences were observed in the forebrain following either treatment. In hypothyroid rat cerebellum, a single injection of triiodothyronine (T3, 100 μg/100 g 18 h before sacrifice) increased significantly ODC activity at all ages. A dose–response study showed that 0.5 μg T3/100 g is sufficient to obtain maximal stimulation. Finally, administration of antiserum against rat growth hormone had no significant effect on ODC response to T3. These results show that ODC is a useful marker of thyroid state and tissue response in the neonatal rat cerebellum.
Ah receptor in primate liver: binding of 2,3,7,8-trachlrodibenzo-p-dioxin and carcinogenic aromatic hydrocarbons
Authors: Okey Allan B. , Vella Lynn M. , Iverson Frank
Published: April 2011

Ah receptor in hepatic cytosols from adult cynomolgus monkeys (Macaca fasicularis) was identified and quantitated by its binding of the highly toxic chemical 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and the carcinogens 3-methylcholanthrene, benzo[a]pyrene, and dibenz[a,h]anthracene. The concentration of Ah receptor in cynomolgus hepatic cytosols (~10 fmol/mg cytosol protein) was about one-quarter of that typically detected in rodent hepatic cytosols. Receptor concentrations were equal in male and female cynomolgus. [3H]TCDD bound to cytosolic receptor with high affinity (Kd ~ 3 nM). In rodents, Ah receptor is known to play a central role in toxicity caused by halogenated aromatic compounds and in carcinogenesis caused by polycyclic aromatic hydrocarbons. Existence of Ah receptor in monkeys indicates that the receptor also may mediate such responses in primates.
Structural basis for function of circular muscle of canine corpus
Authors: Daniel E. E. , Sakai Y. , Fox J. E. T. , Posey-Daniel V.
Published: April 2011

The structural relationship of nerve, muscle, and interstitial ceils of Cajal in circular muscle of the lesser curvature of the dog stomach (corpus) has been studied. This muscle has also been characterized functionally. Muscle cells are arranged in bundles and are interconnected by numerous gap junctions averaging 30 per 100 cross-sectioned muscle cells, and leading to an estimate that each cell has about 200 gap junctions. No other smooth muscle studied to date has such a high density of gap junctions. Nerve varicosities, mostly containing a predominance of small agranular vesicles with some containing a predominance of large granular vesicles, are located outside muscle bundles, usually in small- to medium-sized bundles. Very few nerves containing small granular vesicles, presumably adrenergic, were found in agreement with functional studies. A substantial number of damaged nerve profiles was also found, perhaps contributing to the loss of nerve-dependent responses present in vivo, but absent in vitro. Interstitial cells of Cajal were rare in this tissue, about 1 per 1000 cross-sectioned muscle cells. When present, they often made gap junction contact with smooth muscle and were closely innervated. The findings of a structural basis for very tight coupling between cells, the absence of a structural basis for direct neural control over motor function, and other findings have implications for the control of contractions in this muscle.
Calcium channel activation in vascular smooth muscle by BAY K 8644
Authors: Su C. M. , Swamy V. C. , Triggle D. J.
Published: April 2011

BAY K 8644 (methyl-1,4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoromethylphenyl)pyridine-5-carboxylate) and CGP 28 392 (ethyl-4(2-difluoromethoxyphenyl)-1,4,5,7-tetrahydro-2-methyl-5-oxofuro-[3,4-b]pyridine-3-carboxylate) are closely related in structure to nifedipine and other 1,4-dihydropyridine Ca2+ channel antagonists. However, both BAY K 8644 and CGP 28 392 serve as activators of Ca2+ channels. In the rat tail artery, responses to BAY K 8644 are dependent upon [Formula: see text] and prior stimulation by K+ or by the α-adrenoceptor agonists, phenylephrine and BHT 920 (6-allyl-2-amino-5,6,7,8,-tetrahydro-4H-thiazolo[4,5-d]azepin dihydrochloride). Responses are blocked noncompetitively by the Ca2+ channel antagonists D-600 ((−)-D-600 > (+)-D-600) and diltiazem, but competitively by nifedipine (pA2 = 8.27). This suggests that activator and inhibitor 1,4-dihydropyridines interact at the same site. BAY K 8644 potentiates K+ responses and Ca2+ responses in K+-depolarizing media. The leftward shift of the K+ dose–response curve produced by BAY K 8644 suggests that this ligand facilitates the voltage-dependent activation of the Ca2+ channel. The pA2 value for nifedipine antagonism of BAY K 8644 responses is significantly lower than that for nifedipine antagonism of Ca2+ responses in K+ (25–80 mM) depolarizing media (9.4–9.6), suggesting that the state of the channel may differ according to the activating stimulus.
Impaired diluting capacity of the thick ascending limb during loop bicarbonate and nitrate perfusion in vivo
Authors: Gutsche Hans-Ulrich , Peterson Linda N. , Sauerwald Karl-Heinz , Levine David Z.
Published: April 2011

Previous whole animal studies have indicated that when nitrate or bicarbonate is substituted for chloride, renal concentrating defects can be demonstrated. It has been proposed that function of the "distal nephron" or thick ascending limb may be impaired when chloride is replaced by other anions. To examine this proposal, microstop-flow experiments were performed in rats in which loops were perfused with solutions containing 110 mM NaCl, NaHCO3, or NaNO3. Solute reabsorption by the thick ascending limb was assessed by measuring the minimum conductivity of fluid emerging from the loop following intervals of stop-flow. Thick ascending limb solute transport was impaired in loops perfused with HCO3 or NO3 evidenced by the marked increase in solute remaining in the loop after 60 s of stop-flow. The calculated corresponding sodium concentrations were in the range of 17–24 mM Na for the NaCl perfusion, 57–88 mM Na for the NaHCO3 perfusion, and 57–69 mM Na for the NaNO3 perfusion. Clearly, the minimum concentration achieved with NaCl was approximately one-third of that reached with the nitrate or bicarbonate solutions. These results indicate that when chloride-poor solutions reach the thick ascending limb, an important impairment of diluting capacity is demonstrable in vivo in the rat. The present studies, therefore, provide an important link between recent information regarding the mechanism of NaCl transport in the thick ascending limb and older whole animal studies suggesting an important role for distal chloride delivery in urine concentration.
Cardiomyopathic hamsters, CHF 146 and CHF 147: a preliminary study
Authors: Hunter E. G. , Hughes V. , White J.
Published: April 2011

The time course and characteristics of lesion development in both cardiac and skeletal muscle from two strains of cardiomyopathic hamsters (CHF 146 and CHF 147) were studied by histological methods. The chronology of lesion development and the histological characteristics of the lesions were similar in both strains. However, increased calcification of cardiac lesions was present in the hearts of CHF 147 animals. This may account for the difference in lifespan between the CHF 147 (350 days) and the CHF 146 (440 days).
Effect of strontium on the contractile properties of postnatally developing rat heart ventricles
Authors: Vornanen Matti
Published: April 2011

The effects of substitution of calcium (Ca) by an equimolar concentration of strontium (Sr) on isometric contractions of isolated ventricular muscle from postnatally developing rat heart were studied. The duration of contraction and the time-to-peak tension were increased in all age groups although much less in the adult rats than in the neonates. The contractile force was increased in the muscles of rats between 1 and 14 days of age but was depressed in the older animals. The prominent rest-twitch potentiation of neonatal rat heart in Ca− Tyrode was totally eliminated by Sr, whereas a clear rest-twitch potentiation was induced by this cation in the adult rat heart, in which tissue the potentiation is normally absent in Ca− Tyrode. The maximal twitch potentiation by rest in Ca− Tyrode and the positive inotropic effect of Sr substitution grew from birth up to day 9 and from then gradually declined towards the level of adult rat heart by the end of the 3rd postnatal week. The phase of increasing rest-twitch potentiation coincides fairly well with the known development of sarcoplasmic reticulum and the phase of decline with the appearance of the T system of the sarcolemma. It is suggested that the qualitative changes in the contractile properties of developing rat heart during the 3rd postnatal week are due to the more efficient utilization of intracellular calcium stores, owing to the development of the T system.
Potentiation of β-endorphin effects by cholecystokinin antiserum in rats
Authors: Itoh Shinji , Katsuura Goro , Yoshikawa Kenji , Rehfeld Jens F.
Published: April 2011

Intracerebroventricular administration of a C-terminal cholecystokinin (CCK) antiserum potentiated the analgesic and cataleptic effects of (β-endorphin. The results are opposite to those observed after injection of CCK-8. It was suggested that CCK-8 may play a physiological role antagonizing the action of β-endorphin.
Effect of calcitonin on fractional delivery of sodium and solutes to the juxtamedullary end-descending limb of the rat
Authors: Roy Denis R.
Published: April 2011

The purpose of the present studies was to examine, by micropuncture, the effect of salmon calcitonin on fractional sodium and solutes deliveries to the juxtamedullary end-descending limb of the rat. All animals were postprandial and thyro-parathyroidectomized Munich-Wistar rats. Group 1 (N = 8) consisted of time control water-diuretic rats; group 2 (N = 8) received synthetic salmon calcitonin (10 mU/min) intravenously while undergoing water diuresis; group 3 (N = 8) was treated as group 2 but also received calcium intravenously to prevent the calcitonin-induced fall in plasma calcium. Calcitonin, alone and with calcium, produced a marked fall in urine flow rate and a marked increase in urinary osmolality. Concomitant fractional water delivery to the end-descending limb fell significantly (28 ± 0.8 to 21 ± 1.0%, p < 0.05), while fractional solute and sodium deliveries increased significantly (36 ± 1.3 to 55 ± 2.6%, p < 0.05; 34 ± 2.0 to 48 ± 3.5%, p < 0.05, respectively). The three groups did not significantly differ in fractional water and sodium deliveries to the superficial end-accessible proximal tubule. We conclude that salmon calcitonin is antidiuretic in the rat and that it also produces an increase in fractional sodium and total solute deliveries to the end-descending limb, which we suggest is due to transepithelial sodium addition. The physiological significance of these observations to water homeostasis in vivo remains to be determined.
Renal response to hemorrhage in dogs with subacute biliary obstruction
Authors: Levy Mortimer , Fechner Christine
Published: April 2011

In the present study, we tested the hemodynamic and renal response of 15 sham-operated dogs and 15 dogs with subacute (5–9 days) biliary obstruction to either acute or more chronic hemorrhage. All studies were conducted on sedated but unanaesthetized animals. Both groups were comparable before blood withdrawal with respect to central hemodynamics and renal perfusion. Serum bilirubin was 0.70 ± 0.09 mg/dL for control dogs and 8.25 ± 0.14 for experimental dogs (P < 0.05). In the acute protocol, nine control and seven jaundiced dogs were bled over a period of 30–40 min to lower blood pressure by 19.1 and 19.5%, respectively. Blood volumes required to achieve this drop were 21.3 and 20.05 mL/kg, respectively (P > 0.05). Cardiac output declined by an equivalent value for each group and glomerular filtration rate and clearance of p-arninohippurate remained unchanged from control values. In six control and eight experimental dogs, 500 mL of blood was withdrawn over 5 days. Although blood pressure and cardiac output declined for each group by an equivalent amount, renal perfusion remained unchanged for each group from control values. We conclude that acute or chronic hemorrhage of modest degree does not predispose to acute renal insufficiency in dogs with subacute biliary obstruction.
Oesophageal peristalsis in the cat: the role of central innervation assessed by transient vagal blockade
Authors: Reynolds R. P. E. , El-Sharkawy T. Y. , Diamant N. E.
Published: April 2011

Studies were performed on five cats to assess the role of extrinsic vagal innervation in the control of peristalsis in the smooth muscle oesophagus. Transient vagal nerve blockade was accomplished by cooling the cervical vagosympathetic nerve trunks previously isolated in skin loops on each side of the neck. Peristalsis throughout the body of the oesophagus was monitored using a continuously perfused multilumen manometry tube. Striated and smooth muscle portions of the esophagus were delineated by abolishing smooth muscle activity with atropine. Secondary peristalsis was assessed by intra-oesophageal balloon distension studies. The threshold volume for balloon-induced secondary peristalsis was lower in the smooth muscle oesophagus. Unilateral vagal blockade reduced the incidence of primary and secondary peristalsis in the striated muscle oesophagus but not in the smooth muscle oesophagus. Bilateral vagal nerve blockade abolished primary swallow-induced peristalsis and secondary peristalsis in both the smooth and striated muscle cat oesophagus. Administration of cholinergic agents or adrenergic blocking agents failed to restore secondary peristalsis in the smooth muscle oesophagus during vagal cooling. We conclude that connections to the central nervous system via the vagal nerve trunks are required for normal secondary as well as primary peristalsis in both the smooth and striated muscle portions of the cat oesophagus.
Pulmonary vascular responsiveness in cold-exposed calves
Authors: Greenlees K. J. , Tucker A. , Robertshaw D. , Vader C. R.
Published: April 2011

The pulmonary vascular responses to acute hypoxia and to infusions of histamine and 5-hydroxytryptamine (5-HT) were recorded in unanesthetized standing bull calves under neutral (16–18 °C) and cold (3−5 °C) temperature conditions. Cold exposure alone resulted in a significant increase in pulmonary arterial wedge pressure from 10.2 ± 3.5 to 15.9 ± 4.9 Torr (1 Torr = 133.322 Pa). Resistance to blood flow between the pulmonary wedge and the left atrium significantly increased from 0.50 ± 0.51 to 1.21 ± 0.78 mmHg∙L−1∙min−1 (1 mmHg = 133.322 Pa) with cold exposure. This apparent pulmonary venoconstrictor response to cold exposure was further evaluated to determine if hypoxia, histamine, or 5-HT responsiveness was altered by cold exposure. Twelve minutes of hypoxia increased pulmonary arterial and systemic arterial pressures, heart rate, and respiratory rate similarly in cold and neutral temperatures. Cold exposure did not alter the dose-related reductions of systemic arterial and pulmonary arterial pressures in response to histamine. Similarly, the decreases in systemic arterial pressure and heart rate and increases in pulmonary arterial and left atrial pressures in response to 5-HT were not significantly different in cold and neutral conditions. It was concluded that acute, mild cold exposure results in an increase in resistance to blood flow in the pulmonary venous circulation without a general increase in pulmonary vascular reactivity, as measured by responses to hypoxia, histamine, and 5-HT.
Effect of weaning on the activities of glycogen synthase and phosphorylase in rat liver
Authors: Khandelwal Ramji L. , Braun Ralph P. , Angel Joseph F.
Published: April 2011

The effects of weaning on the level of glycogen and the activities of glycogen synthase and phosphorylase were determined in rat liver. Glycogen levels in rat liver increased at the start of the weaning period and reached a plateau on postnatal day 20. The active form of glycogen synthase increased until postnatal day 19 and then declined. Total glycogen synthase (active + inactive) remained high during the suckling period and declined to a new low level during the weaning period. The activity ratio (active/total) increased from day 16 to days 18 – 22 and then decreased to the same level as found during the suckling period. At the onset of weaning the active form of phosphorylase decreased, whereas total phosphorylase initially increased and then decreased after postnatal day 20. Both forms of phosphorylase increased again at the end of the weaning period. The activity ratio decreased at the start of weaning and remained low throughout the rest of the weaning period. The effects of premature weaning were similar to those observed in normally weaned animals, but the changes occurred sooner and were more pronounced.
Vanadium exposure enhances lipid peroxidation in the kidney of rats and mice
Authors: Donaldson John , Hemming Richard , Labella Frank
Published: April 2011

Vanadium (V) as sodium orthovanadate induces an increase in lipid peroxidation in the kidneys after a single subcutaneous or intraperitoneal injection to rats or mice. The rate of malondialdehyde (MDA) formation, an index of lipid peroxidation, by-kidney homogenates increased by more than 100% 1 h after injection. Chronic exposure of rats to vanadium sulfate, initially through maternal milk and later in the drinking water, resulted after 10 weeks in a significant increase in MDA formation by kidney but not by other tissues, in both acute and chronic studies in rats and mice, no significant increase in lipid peroxidation by V treatment was detected in brain, heart, lung, spleen, or liver. In mice, administration of ascorbate prior to acute exposure to V diminished both toxicity, i.e., respiratory depression and limb paralysis, and the formation of MDA in kidney.
Failure of gallamine and pancuronium to inhibit selectively (−)-[3H]quinuclidinyl benzilate binding in guinea-pig atria
Authors: Choo L. K. , Leung E. , Mitchelson F.
Published: April 2011

Binding of (−)-[3H]quinuclidinyl benzilate (QNB) to muscarinie sites in guinea-pig atrial and ileal longitudinal muscle homogenates showed the presence of a single population of binding sites in atria (KD = 41 (32–53) (95% confidence limits) pM; Bmax = 0.225 ± 0.02 pmol/mg protein (3)) and two binding sites in the ileum (KD = 20.9 (8.8–49) pM and 11.3 nM; Bmax = 0.436 ± 0.09 and 11.85 ± 2.63 pmol/mg protein (4), respectively). Atropine, gallamine, and pancuronium displaced (−)-[3H]QNB binding from the high affinity binding sites in the two tissues in a dose-dependent manner with –log Ki values of 8.6, 6.4, and 6.9, respectively, in atria and 8.7, 6.8, and 6.9, respectively, in ileal longitudinal muscle. The lack of selectivity of gallamine and pancuronium in binding experiments differed from results obtained in isolated tissue experiments where these antagonists showed a marked difference in their ability to antagonize cholinomimetics in the two tissues. In addition, the Ki values for gallamine and pancuronium in ileal homogenates were ca. 130- and 16-fold lower, respectively, than their KB values determined from isolated tissue experiments. Attempts to correlate data from binding experiments and isolated tissue experiments using combinations of antagonists led to variable results attributed to differences in the rates of dissociation of the antagonists from muscarinic receptors. It is concluded that the interaction of gallamine or pancuronium with agonists or antagonists at muscarinic receptors is not a simple bimolecular interaction.
Mechanisms of gonadotropin-releasing hormone and prostaglandin action on luteal cells
Authors: Leung Peter C. K.
Published: April 2011

Both gonadotropin-releasing hormone (GnRH) and prostaglandin F2α (PGF2α) can inhibit cAMP and progesterone production in the corpus luteum; however, their mechanism of action is not known. GnRH or PGF2α causes a rapid and marked increase of labelling of phosphatidylinositol (PI) and phosphatidic acid (PA) in rat luteal cells in culture. The incorporation of radioactivity is increased as early as 2 and 5 min into PA and PI, respectively. The labelling of the other phospholipids is not affected. GnRH and PGF2α exert their stimulatory effects on PA–PI turnover at a mean effective dose value of ca. 15 and 100 nM, respectively. Their effects appeared to be additive when both agents were present in the same incubations. Interestingly, addition of the calcium ionophore A23187 also causes a dramatic increase of PA–PI turnover in luteal cells. By contrast, human chorionic gonadotropin and isoproterenol, agents that stimulate cAMP and progesterone production in luteal cells, as well as PGE2 (1 μM), all fail to alter phospholipid labelling; dibutyryl or 8-bromo-cAMP (2–5 mM) actually attentuates the GnRH or PGF2α effect on PI and PA. A very similar PA–PI response to GnRH and PGF2α has also been observed using rat granulosa cells in culture. It seems that following their binding to membrane receptors, GnRH and PGF2α may share a common mechanism in the ovarian cell, possibly involving the stimulation of PA–PI metabolism.