bluuebunny/crossref_metadata_2025_split huggingface dataset:
NATURE OF THE β‐ADRENORECEPTORS IN THE TRACHEAL SMOOTH MUSCLE OF THE ADULT PIG
Authors: AGARWAL O. P. , SHARMA J. N. , SIDDIQUI H. H. , GROVER J. K. , GUPTA S. P. , MANCHANDA S. C. 
Published: January 2008

Relaxant responses to isoprenaline (ISO), adrenaline (ADR) and noradrenaline (NA) were investigated on carbachol‐contracted, isolated tracheal smooth muscle preparations of the adult pig to determine the nature of the β‐adrenoreceptors present.
The order of relaxant potencies of the catecholamines on this preparation was ISO>ADR>NA. The potency ratio at 37°C was 1:0.06:0.005. This suggests that β‐adrenoreceptors predominate in isolated tracheal smooth muscle of the adult pig.
Though the order of potency for the above catecholamines did not change, at the lower temperatures of 29° and 33°C, the potency ratios were slightly modified to 1:0.098:0.004 and 1:0.07:0.004 respectively.
pA values on pig tracheal smooth muscle were 8.65 and 9.13 respectively, for the non‐selective β‐blockers propranolol and alprenolol, and 5.63, 5.20 and 6.26 respectively, for the β, selective blockers practolol, atenolol and metoprolol and 6.82 for the β selective β‐blocker, H 35/25. The results suggest the existence and predominance of β2‐adrenoreceptors in tracheal smooth muscle of the adult pig.
Effects of DA‐1‐ and DA‐2‐dopamine antagonists on apomorphine‐induced inhibition of peripheral sympathetic neurotransmission
Authors: Hietala J. 
Published: January 2008

1 Apomorphine, a dopamine receptor agonist, caused a dose‐dependent inhibition of the electrically induced increase in diastolic blood pressure in the pithed rat. The anti‐apomorphine effects of a range of dopamine antagonists with different DA‐1/DA‐2 selectivities were evaluated to characterize the dopamine receptor subtype(s) involved in this response.2 Selective DA‐2 antagonists domperidone and (‐)‐sulpiride and combined DA‐2/DA‐1 antagonists haloperidol, fluphenazine and (+)‐sulpiride were active in this model, whereas the DA‐1 antagonist SCH 23390 and the a‐2 adrenoceptor antagonist idazoxan (RX‐781094) were inactive. The rank order of potency of the dopamine antagonists was domperidone > fluphenazine ≥ (‐)‐sulpiride‐haloperidol>(+)‐sulpiride>SCH 23390. (‐)‐Sulpiride was about 25 times more potent than the (+)‐isomer.3 The observed antagonist profile suggests that the apomorphine‐induced inhibition of neurogenic vasoconstriction in the pithed rat is mediated via dopamine receptors of the DA‐2 subtype. The sympatho‐inhibitory dopamine receptors in the cat heart have similar pharmacological characteristics.4 The dopamine antagonists were devoid of influences on the vasoconstrictor response to electrical stimulation in the absence of apomorphine, whereas idazoxan potentiated it. This provides evidence against the participation of dopamine receptors in the modulation of the vasoconstrictor response to sympathetic stimulation in the pithed rat model.
Prejunctional α2‐adrenoreceptors modulate the stimulated release of noradrenaline in isolated follicle strips from bovine ovaries
Authors: Kannisto P. , Owman Ch. 
Published: January 2008

1 Strips from the follicle wall of bovine ovaries were incubated in Krebs‐Ringer solution containing 3H‐noradrenaline for measurement of transmitter liberation during electrical field stimulation (5 Hz frequency, 1 ms pulse duration, 10 V between the electrodes). The effects of noradrenaline as well as selective α‐adrenoreceptor agonists and antagonists were studied on the electrically induced efflux of radioactivity.2 Noradrenaline (1 μM) inhibited the stimulated release of radioactivity. The α2‐adrenoreceptor agonist, oxymetazoline, significantly reduced the release of radioactivity in concentrations as low as 0.01 μM. The α1‐adrenoreceptor agonist, phenylephrine (0.01–1 μm), was without significant effect.3 Phentolamine (0.01–1 μm) and the selective α2‐adrenoreceptor antagonist, idazoxan (0.01–1 μm) significantly enhanced the electrically evoked release. The α1‐adrenoreceptor antagonist, prazosin (0.01–1 μm), was without effect. Idazoxan (0.1 μm) reversed the inhibitory effect of oxymetazoline (0.1 μm).4 It is concluded that administration of noradrenaline or the α2‐adrenoreceptor agonists reduces the release of labelled noradrenaline by acting on prejunctional α2‐adrenoreceptors in the noradrenergic nerves distributed in the wall of the bovine ovarian follicle. This is one of several prejunctional receptor mechanisms that modulate the activity of the sympathetic nerves innervating the smooth musculature of the follicle wall.
Interactions between calcium channel blockers and α‐adrenoceptors in the human coronary and mammary arteries: a radioligand binding study
Authors: Bronzetti E. , Felici L. , Polidori C. , Amenta F. 
Published: January 2008

1 The study was designed to assess whether Ca2+ channel blockers of the dihydropyridine family (felodipine, nicardipine, nifedipine, nimodipine, nitrendepine and nisoldipine), and of the phenylalkylamine family (verapamil) have any effect on α‐adrenoceptor binding to sections of the human right coronary and mammary arteries, measured using [3H]‐dihydroergocryptine (DHT) as a ligand.2 Increasing concentrations of nicardipine, verapamil and nitrendepine competed with [3H]‐DHT binding to sections of the human coronary and mammary arteries. The other compounds tested were without effect. Among the competitors of [3H]‐DHT binding, nicardipine was the most powerful, with a 50% inhibition (IC50) value of approximately 10 nM.3 The pharmacological profile of competition with [3H]‐DHT binding by nicardipine, in the presence or in the absence of guanosine triphosphate and NaCl, is consistent with antagonist activity of the dihydropyridine derivative at the α‐adrenoceptor.4 This property may account for the lower sympathetic stimulatory activity elicited by nicardipine, in comparison with other Ca2+ channel blockers used in cardiovascular therapy.
The effects of racemic cromakalim, BRL 38226 and levcromakalim on the membrane potential of the rat aorta and of BRL 38226 on the contractile activity of the rat aorta and portal vein
Authors: Bishop Brett E. , Doggrell Sheila A. 
Published: January 2008

1 The effects of racemic cromakalim and the (+)‐3R,4S and (‐)‐3S,4R isomers, BRL 38226 and levcromakalim respectively, on the membrane potential of the rat aorta have been determined. In addition, preliminary studies of the effects of BRL 38226 on the contractility of the rat aorta and portal vein have been made.2 The rat aorta is hyperpolarized by racemic cromakalim at 10 μm and by levcromakalim at 1 μm, but is depolarized by BRL 38226 at 1 μm.3 In the presence of depolarization with 20 μm KCl, racemic cromakalim and levcromakalim, but not BRL 38226, reversed the depolarization of the rat aorta.4 In the presence of hyperpolarization with isoprenaline at 1 μm or in a CaCl2‐free Krebs solution, racemic cromakalim and BRL 38226, but not levcromakalim reversed the hyperpolarization.5 Glibenclarnide at 0.3 and 1 μm depolarized the rat aorta. Pretreatment with glibenclamide at 1 μm prevented the hyperpolarizing action of racemic cromakalim but did not alter the depolarizing action of BRL 38226. Pretreatment with BRL 38226 at 10 μm also prevented the hyperpolarizing action of racemic cromakalim.6 Contractility studies demonstrated that BRL 38226 and glibenclamide have no effect on the resting tone of the rat aorta in normal Krebs solution. However in a CaCl2‐free Krebs solution, BRL 38226 and glibenclamide, 0.1–100 μm, caused small contractions. BRL 38226 and glibenclamide increased the spontaneous contractile activity of the rat portal vein in normal Krebs solution.7 The present study illustrates that levcromakalim opens the ATP‐dependent potassium channels of the rat aorta to cause hyperpolarization. BRL 38226 and glibenclamide produce depolarization and contraction of the rat aorta and increase the contractile activity of the rat portal vein, possibly by blocking the ATP‐dependent potassium channels.
Contraction of the sheep middle cerebral, pulmonary and coronary arteries initiated by release of intracellular calcium
Authors: Drummond R. M. , Wadsworth R. M. 
Published: January 2008

1 The aim of the study was to compare contraction initiated by intracellular Ca2+ release in the middle cerebral, coronary and pulmonary arteries of the sheep. With all three arteries from the sheep, incubation in Ca2+‐free physiological salt solution (PSS) reduced agonist‐induced contraction much more than occurred with the rabbit aorta. The intracellular Ca2+ store appeared to be of limited capacity, since contraction was transient in Ca2+‐free conditions with most agonists.2 In the middle cerebral artery, contraction in Ca2+‐free conditions was much reduced if a previous contraction had been obtained (for 5‐hydroxytryptamine, 5‐HT, from 11 + 4 to 1 + 0.5% of control contraction in 2.5 mm Ca2+), suggesting that the previous contraction had partly discharged the intracellular Ca2+ store. Contraction was less affected in the pulmonary artery and almost unaffected in the coronary artery (for 5‐HT, from 15 + 1 to 11 + 1%) by a previous contraction in Ca2+‐free conditions.3 Rings prepared from small branches of the pulmonary and coronary arteries were affected by Ca2+ deprivation in a similar manner to large diameter pulmonary and coronary artery rings.4 In Ca2+‐free PSS, contraction induced by prostaglandin E2 was almost eliminated (3 + 1% of control contraction in 2.5 mm Ca2+), contractions induced by 5‐HT and noradrenaline were reduced, and contraction induced by the thromboxane mimetic U46619 was least affected (up to 73 + 8%).5 Increasing agonist concentration from EC50 to the maximally effective concentration raised the percentage contraction remaining in the middle cerebral artery (for noradrenaline from 7 + 2% to 12 + 3%) but not in the pulmonary artery (for noradrenaline from 22 + 2% to 24 + 6%).6 The present study has revealed notable differences, in coupling to intracellular Ca2+ release between the three vascular territories studied.
Tetraethylammonium selectively stimulates secretion from noradrenergic bovine chromaffin cells
Authors: Cahill Anne L. , Perlman Robert L. 
Published: January 2008

1 The effects of tetraethylammonium chloride (TEA) on catecholamine secretion from primary cultures of noradrenaline‐rich (noradrenergic) and adrenaline‐rich (adrenergic) bovine chromaffin cells were studied. TEA stimulated catecholamine secretion from both cell types but was a much more effective secretory stimulus for noradrenergic cells.2 TEA‐induced catecholamine secretion was dependent on extracellular Ca2+, was partially inhibited by nifedipine and by tetrodotoxin, and was potentiated by ouabain. Other K+ channel blocking agents including 4‐aminopyridine, glibenclamide, and tolbutamide did not stimulate catecholamine secretion.3 TEA had no effect on Ca2+‐induced secretion from digitonin‐permeabilized chromaffin cells.4 TEA presumably evokes secretion by inhibiting K+ channels, depolarizing chromaffin cells, and activating voltage‐gated Ca2+ channels in the cells. Noradrenergic cells appear to be more sensitive to K+ channel inhibition than are adrenergic cells.5 The secretory response of the chromaffin cells to TEA increased with time in culture.6 In addition to being a more effective secretagogue in noradrenergic cells, TEA was also more effective in stimulating catecholamine synthesis in these cells.
Dopamine‐induced inhibition of endogenous acetylcholine release from the isolated ileal synaptosomal preparations of guinea‐pig mediated via α‐adrenoceptors
Authors: Chang Shu‐Shi , Cheng Juei‐Tang 
Published: January 2008

1 The effect of exogenous dopamine on the release of endogenous acetylcholine (ACh) from isolated ileal synaptosomal guinea‐pig preparations was examined by means of high pressure liquid chromatography with electrochemical detection.2 Release of ACh was induced by substance P or by depolarization with high potassium (50 mM) in a medium containing atropine, propranolol and naloxone.3 Dopamine produced a concentration‐dependent inhibition of the evoked ACh release induced by substance P or in samples depolarized by high potassium. This action of dopamine was not reversed by the dopamine receptor antagonists either for the DA2 subtype, domperidone, or for the DA1 subtype, SCH23390. Fenoldopam, the agonist of dopamine DA1 receptors, or quinpirole, the agonist of dopamine DA2 receptors, reduced the evoked ACh release, although only in high, non‐dopamine‐specific concentrations.4 Failure of guanethidine or desipramine to inhibit this effect of dopamine ruled out mediation by endogenous noradrenaline.5 Idazoxan and yohimbine reversed this dopamine‐induced inhibition at concentrations sufficient to abolish the action of clonidine. Influx of 45Ca stimulated by substance P or high potassium into synaptosomal preparations was attenuated in the presence of dopamine. This inhibition by dopamine was also reversed by idazoxan or yohimbine but not by dopamine receptor antagonists. Moreover, the dopamine‐induced inhibitions of both the ACh release and the influx of 45Ca disappeared in the samples treated with pertussis toxin at a dose sufficient to abolish the action of clonidine.6 It is concluded that dopamine suppresses the influx of calcium ions into cholinergic nerve terminals via an activation of α2‐adrenoceptors coupled with a pertussis toxin‐sensitive GTP‐binding protein, resulting in the decrease of ACh release from ileal synaptosomes of guinea‐pigs.
Non‐adrenergic non‐cholinergic (NANC) excitatory response of the channel catfish intestine
Authors: Venugopalan C. S. , Holmes E. P. , Jarboe H. H. , Kleinow K. M. 
Published: January 2008

1 Optimal parameters for electrical field stimulation (EFS) of catfish pyloric and middle intestinal segments were determined (15 Hz, 60 V) from a range of frequencies (5–45 Hz) and voltages (40–120 V) using a modified Magnus’method. Contractile responses were produced by EFS which were reproducible and showed no significant difference between the tissues.2 The contractile cholinergic responses of the tissues to carbachol and acetylcholine (ACh) were blocked by atropine on an equimolar concentration, whereas, these responses were enhanced in the presence of neostigmine, an acetylcholinesterase inhibitor.3 Adrenergic responses were examined with noradrenaline (NA). NA produced contraction of the segments only, at a concentration of 10−4m. Among the various adrenoceptors, β ‐adrenoceptor stimulation produced a weak relaxation whereas, both α1‐ and α2‐adrenoceptor stimulation produced contractions, of which α2‐induced contraction was of greater magnitude. The β, α1 and α2 responses were blocked by their respective blocking agents propranolol, prazosin and yohimbine.4 The autonomic components of the response to EFS were determined by using selected cholinergic and adrenergic antagonists separately or collectively. Cholinergic blockade with atropine did not produce a significant blockade of the EFS‐induced response. Similarly, blockade of β ‐adrenoceptors with propranolol did not modulate the contractile response to EFS to any significant level. Blockade by prazosin or yohimbine did not significantly change the contractile response to EFS. After a complete blockade of the adrenergic and cholinergic divisions, the intestinal segments still showed a contractile response to EFS which was not significantly different from the control response. This indicated the presence of a non‐adrenergic non‐cholinergic (NANC) response.5 Tetrodotoxin, at 10−6m, significantly blocked the EFS‐induced NANC response suggesting a neurogenic origin for the response.6 The present study indicated that the EFS‐induced response of the catfish intestinal segments is predominantly NANC‐e in nature suggesting an important role for it in the regulation of intestinal motility.
Mechanical and current responses to neurotensin in the smooth muscle of guinea‐pig intestine
Authors: Ohashi H. , Takewaki T. , Unno T. , Komori S. 
Published: January 2008

1 The effects of neurotensin (NT) on the mechanical activity of the smooth muscle and membrane currents of enzymatically‐dispersed single smooth muscle cells of guinea‐pig intestine were investigated by the isometric tension recording method and the whole‐cell patch clamp technique, respectively.2 NT (0.3–670 nm) produced an initial relaxation followed by a contraction in segment preparations of the jejunum and ileum. Atropine (0.2 μm) abolished the contraction. In 30% of ileal segments, NT produced a slowly‐developed contraction in the presence of atropine. The atropine‐resistant contraction was insensitive to tetrodotoxin (TTX, 0.2 μm). The relaxant effect of NT was unaffected by TTX (0.2 μm) and guanethidine (2 μm), but markedly reduced or abolished by apamin (67 nm).3 In segment preparations of the colon and rectum, NT produced a biphasic response, similar to that in the small intestine, or a triphasic one (relaxation, contraction and relaxation). The contractile effect of NT was affected neither by atropine (0.2 μm) nor by TTX (0.2 μm). The first relaxation in response to NT was similar in pharmacological properties to that in the small intestine.4 Responses to NT in longitudinal muscle strips were similar to those in segment preparations. The taenia caecum responded to NT with a contraction alone and the effect was unaffected by atropine (0.2 μm) and TTX (0.2 μm).5 NT had little or no effect on the mechanical activity in the circular muscle of the small intestine. In the circular muscle of the large intestine, NT had a weak inhibitory effect on the spontaneous activity which was followed by a small rise in muscle tone. Apamin (67 nm) converted the biphasic response to a contraction.6 In cells dialysed with a KCl‐based solution under voltage clamp at 0 mV, NT (5 μm) produced a brief, outward current in a very small fraction of cells (4 out of 40 cells). When cells were dialysed with a CsCl‐based solution under voltage clamp at – 50 or – 60 mV, no current response to NT (5 μm) was observed in all 37 cells, but NT increased inward Ca2+ currents evoked upon depolarization.7 From these results, it appears that there is a regional difference in the mode of action of NT to contract and relax the smooth muscle of guinea‐pig intestine, and NT acts on its receptors on the smooth muscle to enhance activation of voltage‐dependent Ca2+ channels, which underlies the slow contraction in the longitudinal muscle of the intestine.
Effect of sympathetic denervation on the relaxing responses of rabbit arterial smooth muscle *
Authors: Villanueva M. M. , Soares‐da‐Silva P. , Osswald W. 
Published: January 2008

1 The present study reports on the influence of chemical denervation by 6‐hydroxy‐dopamine (6‐OHDA) on the relaxing responses to carbachol, sodium nitroprusside, zaprinast, adenosine, forskolin and 3‐isobutyl‐l‐methylxanthine (IBMX) of ring preparations of rabbit renal and femoral arteries.2 Carbachol was found to induce a complete abolition of the tone induced by 5‐hydroxytryptamine (0.1–1.0 μM), both in the renal and the femoral arteries. The profile of the carbachol‐induced relaxation in both the renal and femoral arteries obtained from 6‐OHDA‐treated rabbits was similar to that observed in control animals; relaxing responses obtained with some of the concentrations of carbachol were, however, found to be greater (P< 0.01) in denervated arteries. Sodium nitroprusside was also found to be an effective relaxant agent in both renal and femoral arteries, though more potent in the former but was unaffected by denervation. Zaprinast relaxed both renal and femoral artery ring preparations, and again, no significant difference was observed between control and denervated animals.3 The cyclic AMP‐mediated relaxing responses to adenosine, forskolin and IBMX were found to be similar in renal and femoral arteries of control arteries, producing almost complete abolition of pre‐existing tone. The adenosine‐ and IBMX‐induced relaxing responses in renal and femoral arteries were found to be similar in control and denervated animals. However, the concentration–response curve to forskolin was shifted to the left by 2.5 and 1.5 log units in preparations of renal and femoral arteries of denervated rabbits, respectively.4 The results presented here suggest that: (1) the basal production of cyclic GMP does not appear to be different in the two arteries, but differences in the generation of EDRF or in the activity of guanylate cyclase appear to exist; (2) the basal production of cyclic AMP is of about the same magnitude in the two arteries, and the same applies to adenylate cyclase activity, and finally, (3) sympathetic denervation increases the responses of arterial smooth muscle to activation of adenylate cyclase by forskolin, but not by adenosine.
Muscarinic M3 receptors mediate contractions in rabbit endothelium‐denuded aorta in vitro
Authors: Watson N. , Eglen R. M. 
Published: January 2008

1 Muscarinic receptors mediating contraction of rabbit endothelium‐denuded aorta have been characterized functionally, in vitro, using a range of antagonists (atropine, pirenzepine, methoctramine, himbacine, 4‐diphenyl‐acetoxy‐N‐methyl piperidine methiodide (4‐DAMP) and para‐fluoro‐hexahydro‐siladifenidol (p‐F‐HHSiD).2 The non‐selective muscarinic agonist, (+)cis‐dioxolane, induced concentration‐dependent contractions of endothelium‐denuded aortic rings. The potency (EC50) of (+)cis‐dioxolane was 1.0 ± 0.4 μM and the maximal increase in isometric tension was 944 ± 98 mg (mean ± SEM, n= 25). The concentration–effect curves to (+)cis‐dioxolane were shifted to the right in the presence of antagonists, in a concentration‐dependent manner. The following affinities (– log KB) were calculated; atropine, 9.4; pirenzepine, 6.6; methoctramine, 5.9; himbacine, 7.1; 4‐DAMP, 9.2; and p‐F‐HHSiD, 7.7.3 It is concluded that muscarinic M3 receptors mediate contractions of endothelium‐denuded aorta. The low potency of (+)cis‐dioxolane, when compared to its potency in other M3 receptor assays, suggests that the efficiency of receptor coupling, associated with contraction of this tissue, is poor.
Release of endogenous ATP from the vasa deferentia of the rat and guinea‐pig by the indirect sympathomimetic tyramine
Authors: Kirkpatrick Karen A. , Burnstock G. 
Published: January 2008

1 Adenosine 5′triphosphate (ATP) as well as [3H]‐noradrenaline ([3H]‐NA) is released by perfusion of the vas deferens with the indirect sympathomimetic tyramine (100 μM); this result is consistent with the concept of sympathetic cotransmission.2 While tyramine produced a strong contraction in the vas deferens of the rat, it had little mechanical action in the guinea‐pig vas deferens. This appears to be largely because tyramine induces considerably lower levels of release of both ATP and NA from the guinea‐pig vas deferens compared to that of the rat. Furthermore, NA released by tyramine appears to release ATP from a secondary pool in the rat vans deferens, but not that of the guinea‐pig, since prazosin reduced the tryamine‐induced release of ATP in the rat vas deferens.3 α, β ‐Methylene ATP (α, β ‐meATP) increased both the spontaneous release of ATP and the tyramine‐evoked efflux of ATP and [3H]‐NA. The basal and tyramine‐induced efflux of [3H]‐NA was also enhanced by the α1‐adrenoceptor antagonist, prazosin, suggesting that prejunctional α1‐adrenoceptors may modulate neurotransmitter release.