bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of (8–32) salmon calcitonin, an amylin antagonist, on insulin, glucagon and somatostatin release: study in the perfused pancreas of the rat
Authors: Silvestre R.A. , Salas M. , Rodriguez‐Gallardo J. , Garcia‐Hermida O. , Fontela T. , Marco J. 
Published: July 2012

The 8–32 fragment of salmon calcitonin ((8–32) sCT) has been proposed as a highly selective amylin receptor antagonist.
In the present study, we have studied the influence of (8–32) sCT on the inhibitory effect of both amylin and its structural congener, calcitonin gene‐related peptide (CGRP), on insulin secretion in the rat perfused pancreas.
Both amylin and CGRP, at 75 pM, clearly inhibited glucose‐induced insulin release (by 80% and by 70%, respectively). Simultaneous infusion of 10 μm (8–32) sCT reversed the inhibitory effect of amylin (by 80%; P<0.05 vs. amylin experiments) but did not significantly affect the inhibition of glucose‐induced insulin output elicited by CGRP. Furthermore, at the same concentration (10 μm), (8–32) sCT alone potentiated the insulin response to 7 mM glucose (2.5 fold; P<0.05) whilst it did not affect glucagon or somatostatin secretion.
The observation that infusion of an amylin antagonist into the rat pancreas potentiates the insulin response to glucose, favours the concept of endogenous amylin as an inhibitor of insulin release.
Finally, as an amylin antagonist at the level of the β‐cell, (8–32) sCT might be considered of potential interest in experimental and clinical pharmacology.
Oestradiol‐induced relaxation of rabbit basilar artery by inhibition of voltage‐dependent Ca channels through GTP‐binding protein
Authors: Ogata Rika , Inoue Yoshihito , Nakano Hitoo , Ito Yushi , Kitamura Kenji 
Published: July 2012

Effects of oestradiol on the electrical and mechanical properties of the rabbit basilar artery were investigated by use of microelectrode, patch‐clamp and isometric tension recording methods.
Oestradiol (10 μm‐100 μm) relaxed arterial tissue pre‐contracted by excess [K]0 solution (30 mM) in a concentration‐dependent manner. In Ca‐free solution, histamine (10 μm) and caffeine (20 mM) each produced a phasic contraction, but oestradiol (10 μm) did not significantly affect their amplitude.
Oestradiol (≥ 100 μm) did not change the resting membrane potential of the artery whether in the presence or absence of TEA (10 mM). Action potentials observed in the presence of 10 mM TEA were abolished by oestradiol (100 μm).
Oestradiol (1 μm‐100 μm) inhibited the voltage‐dependent Ba current in a concentration‐dependent manner. Oestradiol (100 μm) inhibited the Ba current observed in the presence of nicardipine (1 μm) more than that in the absence of nicardipine (to 31.0% vs 62.0% of control).
GTPγS (30 μm) in the pipette enhanced the inhibitory actions of oestradiol on the Ba current. On the other hand, with GDPβS (1 mM) in the pipette, oestradiol failed to inhibit the Ba current. Pertussis toxin (PTX 3 μg ml−1) in the pipette totally prevented the inhibitory action of oestradiol on the Ba current.
Oestradiol (≷ 100 μm) had no significant effect on the outward K currents evoked by a membrane depolarization.
These results strongly suggest that oestradiol relaxes arterial tissue by inhibition of voltage‐dependent Ca channels and that it inhibits both nicardipine‐sensitive and‐resistant Ca currents via a PTX‐sensitive GTP‐binding protein. The main target of oestradiol among the arterial Ca channels seems to be the nicardipine‐resistant Ca channel, rather than the nicardipine‐sensitive one.
Regulation of nitric oxide‐like activity by prostanoids in smooth muscle of the canine saphenous vein
Authors: Illiano Stephane , Marsault Robert , Descombes Jean‐Jacques , Verbeuren Tony , Vanhoutte Paul M. 
Published: July 2012

Organ bath experiments and measurements of prostanoids were performed to investigate the presence of nitric oxide synthase in venous smooth muscle and its interaction with cyclo‐oxygenase.
In rings of canine saphenous vein without endothelium, the inhibitor of cyclo‐oxygenase, indomethacin (10 μm), induced contraction. NG‐nitro‐L‐arginine (100 μm) (L‐NOARG), an inhibitor of nitric oxide synthase did not affect the tone of rings of canine saphenous vein when administered alone. However, in the presence of indomethacin L‐NOARG (100 μm) induced further contraction.
Similar results were obtained in response to NG‐monomethyl‐L‐arginine (L‐NMMA)(300 μm or NG‐nitro‐L‐arginine methylester (L‐NAME)(100 μm).
When rings of canine saphenous vein without endothelium were contracted with phenylephrine (1 μm) instead of indomethacin, neither L‐NOARG or L‐NMMA induced further contraction.
When rings of canine saphenous vein without endothelium were contracted with noradrenaline (0.3 μm) in the presence of indomethacin (10 μm) plus L‐NOARG (100 μm), a relaxation to L‐arginine was observed. Transient relaxations to superoxide dismutase (150 u ml−1) were observed in all rings.
When rings of saphenous vein without endothelium were incubated with lipopolysaccharide (LPS) (100 μg ml−1) or interleukin −1β (10 u ml−1) the concentration‐contraction curve to noradrenaline was not affected.
Rings without endothelium released prostaglandin E2 and prostaglandin I2, as measured by radiommunoassay. The basal production was abolished by indomethacin and not affected by L‐NOARG.
These results suggest that when cyclo‐oxygenase is inhibited, a nitric oxide synthase activity is revealed in rings of canine saphenous vein without endothelium.
Mechanism of butyrate‐induced vasorelaxation of rat mesenteric resistance artery
Authors: Aaronson P.I. , McKinnon W. , Poston L. 
Published: July 2012

The vasorelaxant effect of the sodium salt of the short chain fatty acid, butyrate, on preconstricted rat small mesenteric arteries (mean inner diameter approximately 300 μm) was characterized. Isometric force development was measured with a myograph, and intracellular pH (pHi) was simultaneously monitored, in arteries loaded with the fluorescent dye BCECF in its acetomethoxy form. Sodium butyrate (substituted isosmotically for NaCl) was applied to arteries after noradrenaline (NA) or high K+ contractures were established.
Arteries preconstricted with a concentration of NA inducing an approximately half maximal contraction were relaxed by 91.5±6.3% by 50 mmol 1−1 butyrate. This concentration of butyrate did not, however, cause a significant relaxation of contractures to a maximal (5 μmol 1−1) NA concentration, and also failed to relax signifcantly contractures stimulated by high (45 and 90 mmol 1−1) K+ solutions. Contractures elicited with a combination of NA (at a submaximal concentration) and 45 mmol 1−1 K+ were, however, markedly relaxed by butyrate.
Investigation of the concentration‐dependency of the butyrate‐induced relaxation of the half maximal NA response revealed an EC50 for butyrate of approximately 22 mmol 1−1.
Sodium butyrate (50 mmol 1−1) caused pHi to decrease from 7.25±0.02 to 6.89±0.08 (n=4, P<0.001). However, the vasorelaxant effect of butyrate on the submaximal NA contracture was not significantly modified when this fall in intracellular pH was prevented by the simultaneous application of NH4Cl.
Butyrate‐induced relaxation was also unaffected by endothelial denudation and inhibition of NO synthase with Nω‐nitro‐L‐arginine methyl ester (100 μmol 1−1).
The relaxation of the NA contracture by 50 mmol 1−1 sodium butyrate was abolished in arteries pretreated with the cyclic AMP antagonist Rp‐cAMPS (25 μmol 1−1).
We conclude that the butyrate‐induced relaxation of the NA contracture is independent of intracellular acidification. The ability of Rp‐cAMPS to abolish the butyrate relaxation indicates that stimulation of the cyclic AMP second messenger system may play an important role in mediating this effect.
Functional characterization of the 5‐HT terminal autoreceptor in the guinea‐pig brain cortex
Authors: Roberts Claire , Watson; Jeannette , Burton; Melanie , Price; Gary W. , Jones Brian J. 
Published: July 2012

In guinea‐pig cerebral cortical slices in vitro we have shown that the rank order of potency of 5‐hydroxytryptamine (5‐HT), 5‐carboxamidotryptamine and sumatriptan for inhibition of electrically stimulated [3H]‐5‐HT release correlates well with published data on their 5‐HT1D receptor binding affinites.
Both the non‐selective 5‐HT1D receptor antagonist, methiothepin and the selective 5‐HT1D receptor antagonist, N‐[4‐methoxy‐3‐(4‐methyl‐1‐piperazinyl]phenyl]‐2′‐methyl‐4′‐(5‐methyl‐1,2,4‐oxadiazole‐3‐yl) [1,1‐biphenyl]4‐carboxamide (GR127935) increased stimulated [3H]‐5‐HT release per se and also attenuated agonist‐induced inhibition of [3H]‐5‐HT release. GR127935 (10nM‐100nM) produced a pA2 of 9.0 against 5‐HT, which is consistent with its 5‐HT1D receptor binding affinity.
From these findings we conclude that, in guinea‐pig cerebral cortex, the 5‐HT terminal autoreceptor is of the 5‐HT1D receptor subtype. However, three observations suggest the presence of multiple terminal autoreceptors: shallow inhibition curves to the agonists; a shallow Schild slope of GR127935 antagonism and differences in the maximal responses to 5‐HT between whole cortex and frontal cortex.
Selection of distinct conformational states of the 5‐HT3 receptor by full and partial agonists
Authors: van Hooft Johannes A. , Vijverberg Henk P.M. 
Published: July 2012

5‐Hydroxytryptamine 5‐HT3 receptor‐mediated ion currents evoked by 5‐HT, quaternary 5‐HT (5‐HTQ), meta‐chlorophenylbiguanide (mCPBG), dopamine and tryptamine in N1E‐115 mouse neuroblastoma cells have been investigated in whole‐cell voltage clamp and single channel patch clamp experiments.
The concentration‐dependent activation and desensitization of the ion currents evoked by the agonists yield the potency order: mCPBG > 5‐HTQ  5‐HT > > tryptamine > dopamine, and the efficacy order: 5‐HT  mCPBG  5‐HTQ > > dopamine  tryptamine. Thus, 5‐HT, 5‐HTQ and mCPBG are full agonists, whereas dopamine and tryptamine are partial agonists at the 5‐HT3 receptor.
Full and partial agonists cause complete cross‐desensitization and activate single channels with similar conductances and open lifetimes. This shows that full and partial agonists act on the same population of 5‐HT3 receptors.
The time course of recovery from desensitization depends on the agonist used. Recovery from partial agonist‐induced desensitization is single exponential, whereas the desensitization induced by full agonists recovers with sigmoid kinetics, suggesting at least 3 steps between 4 states.
During the process of recovery from cross‐desensitization, the full agonists activate a larger fraction of the 5‐HT3 receptors than the partial agonists, irrespective of the agonist used to induce desensitization.
It is concluded that full and partial agonists induce distinct desensitized states and, during recovery from desensitization, recognize distinct conformations of unoccupied 5‐HT3 receptors. This conformational selection is likely to account for the different efficacies of full and partial 5‐HT3, receptor agonists.
Effects of levodropropizine on vagal afferent C‐fibres in the cat
Authors: Shams H. , Daffonchio L. , Scheid P. 
Published: July 2012

Levodropropizine (LVDP) is an effective antitussive drug. Its effects on single‐unit discharge of vagal afferent C‐fibres were tested in anaesthetized cats to assess whether an inhibition of vagal C‐fibres is involved in its antitussive properties. Vagal C‐fibres, identified by their response to phenylbiguanide (PBG), were recorded via suction electrodes from the distal part of the cut vagus. Based on their response to lung inflation, C‐fibres were classified as pulmonary (19 fibres) or non‐pulmonary (6 fibres).
PBG increased the discharge rate of both C‐fibre types and activated a respiratory reflex causing apnoea. This reflex was abolished when the second vagus nerve was cut as well, while PBG‐mediated stimulation of the C‐fibres was not affected by vagotomy.
LVDP was administered intravenously and the C‐fibre response to PBG was compared with that before administration of the drug. LVDP reduced both the duration of apnoea and the response of the C‐fibre to PBG.
Comparison of the C‐fibre responses to PBG and to a mixture of PBG and LVDP revealed that the period of apnoea was shortened and the discharge rate of the C‐fibre reduced when LVDP was present.
The LVDP‐induced inhibition of the C‐fibre response to PBG was on average 50% in pulmonary and 25% in non‐pulmonary fibres.
These results suggest that LVDP significantly reduces the response of vagal C‐fibres to chemical stimuli. It is, thus, likely that the antitussive effect of LVDP is mediated through its inhibitory action on C‐fibres.
Mediation of the positive chronotropic effect of CGP 12177 and cyanopindolol in the pithed rat by atypical β‐adrenoceptors, different from β3‐adrenoceptors
Authors: Malinowska Barbara , Schlicker Eberhard 
Published: July 2012

The influence of β1, β2, and β3‐adrenoceptor agonists and of CGP 12177 and cyanopindolol on heart rate and diastolic blood pressure was studied in the pithed rat.
The β1‐adrenoceptor agonist, prenalterol, increased heart rate and the β2‐adrenoceptor agonist, fenoterol, caused a fall in blood pressure. The effect of prenalterol was antagonized by the β1‐adrenoceptor antagonist, CGP 20712 0.1 μmol kg−1 and the action of fenoterol was attenuated by the β2‐adrenoceptor antagonist, ICI 118551 0.1 μmol kg−1. Both effects were markedly diminished by the non‐selective β‐adrenoceptor antagonist, bupranolol 0.1 μmol kg−1.
The non‐selective β‐adrenoceptor agonist, isoprenaline, three β3‐agonists as well as CGP 12177 and cyanopindolol elicited a positive chronotropic effect, exhibiting the following pEDA60 values (negative log values of the doses increasing heart rate by 60 beats min−1): isoprenaline 10.4, CGP 12177 8.3, cyanopindolol 7.2, BRL 37344 6.9, ZD 2079 5.2 and CL 316243 <5.
CGP 20712 0.1 μmol kg−1, given together with ICI 118551 0.1 μmol kg−1, markedly attenuated the positive chronotropic effect of isoprenaline, BRL 37344, ZD 2079 and CL 316243 without affecting the increase in heart rate produced by CGP 12177 and cyanopindolol.
The positive chronotropic effect of CGP 12177 and cyanopindolol was attenuated by CGP 20712, 1 and 10 μmol kg−1 and bupranolol, 10 μmol kg−1 but was not affected by ICI 118551, 10 μmol kg−1. The effect of CGP 12177 was also not changed by BRL 37344 1 μmol kg−1, ZD 2079 10 μmol kg−1, CL 316243 10 μmol kg−1, the α1‐adrenoceptor antagonist, prazosin 1 μmol kg−1 and the 5‐hydroxytryptamine 5‐HT2A receptor antagonist, ketanserin 3 μmol kg−1.
CGP 12177 0.002 μmol kg−1 and cyanopindolol 0.003 μmol kg−1 shifted to the right the dose‐response curve of prenalterol for its positive chronotropic effect. The ‐log values of the doses causing a twofold shift to the right were 9.6 and 9.5, respectively.
Isoprenaline 0.00001‐0.001 μmol kg−1, BRL 37344 0.01‐1 μmol kg−1 and CGP 12177 0.1 μmol kg−1 caused a fall in diastolic blood pressure which was markedly attenuated by combined administration of CGP 20712 and ICI 118551, 0.1 μmol kg−1 each.
CGP 12177 0.01 and 0.1 μmol kg−1 and cyanopindolol 1 μmol kg−1 elicited an increase in diastolic blood pressure. CGP 20712, ICI 118551, bupranolol and, in the case of CGP 12177, also BRL 37344, ZD 2079, CL 316243, prazosin and ketanserin did not influence this effect.
In conclusion, the positive chronotropic effect of CGP 12177 and cyanopindolol is not mediated via β1‐, β2‐, β3‐, α1‐adrenoceptors or 5‐HT2A receptors. This effect may involve atypical β‐adrenoceptors, similar or identical to those described by Kaumann (1989) in isolated heart preparations.
Hyperpolarization and inhibition of contraction mediated by nitric oxide released from enteric inhibitory neurones in guinea‐ pig taenia coli
Authors: Ward Sean M. , Dalziel Hugh H. , Khoyi Mohammed A. , Westfall Alison S. , Sanders Kenton M. , Westfall David P. 
Published: July 2012

. Inhibition of nitric oxide synthase by NG‐nitro‐L‐arginine (L‐NNA) reduced the neurogenic relaxation of precontracted taenia coli only in the absence of atropine. The membrane hyperpolarization associated with the neurogenic relaxation was also reduced by inhibition of NOS only when atropine was absent.
. The membrane hyperpolarization associated with the neurogenic relaxation of the taenia coli was inhibited by oxyhaemoglobin only in the absence of atropine. In the presence of atropine, oxyhaemoglobin did not reduce the i.j.p. or nerve‐evoked relaxation.
. Inhibition of NOS by L‐NNA did not affect the overflow of [3H]‐ACh in response to electrical field stimulation (EFS), suggesting that, under the conditions of our experiments, endogenous NO did not modulate release of ACh. Sodium nitroprusside also had no effect on the neurogenic overflow of [3H]‐ ACh; however, noradrenaline significantly reduced [3H]‐ACh overflow.
. In summary, the postjunctional effects of neurally‐released NO are not apparent in guinea‐pig taenia coli when atropine is present. This implies muscarinic regulation of NO release or muscarinic regulation of another excitatory substance, such as tachykinin(s), that, when blocked, masks the postjunctional effects of NO. These data, together with previous studies, suggest a possible regulatory role for NO in enteric neurotransmission that may be more prominent in some species or tissues than others.
Enhanced contractile responses of arteries from streptozotocin diabetic rats to sodium fluoride
Authors: Weber Lynn P. , Chow Wing Lim , Abebe Worku , MacLeod Kathleen M. 
Published: July 2012

. Previous studies from this laboratory have demonstrated that α1‐adrenoceptor‐mediated increases in tension and phosphoinositide metabolism are enhanced in the aorta and mesenteric arteries from diabetic rats. The purpose of the present investigation was to determine whether contractile responses to sodium fluoride (NaF), which directly stimulates GTP‐binding proteins (G‐proteins), are also enhanced in diabetic arteries.
. NaF (1–20 mM) in the presence of 10 μm aluminium chloride produced slowly developing, concentration‐dependent contractions in mesenteric arteries from three month streptozotocin‐diabetic (60 mg kg−1, i.v.) male Wistar rats and age‐matched control rats. The maximum contractile response but not the sensitivity to NaF was significantly greater in mesenteric arteries from diabetic than from control rats, as was the response to noradrenaline (NA). Maximum contractile responses of aorta and caudal artery from diabetic rats to NaF were also significantly enhanced.
. Removal of the endothelium and denervation with 6‐hydroxydopamine did not significantly alter the maximum contractile response of mesenteric arteries from either control or diabetic rats to NaF. Similarly, NaF had no effect on cyclic AMP levels in aorta, and no difference in cyclic AMP levels, either basally or in the presence of NaF, was detected between control and diabetic rat aorta.
. Contractile responses of mesenteric arteries from both control and diabetic rats to NaF were diminished in calcium‐free Krebs solution, but the NaF response remained significantly elevated in mesenteric arteries from diabetic rats compared to control.
. Ryanodine (30 μm) which depletes intracellular calcium stores, nifedipine (3 μm) which blocks dihydropyridine‐sensitive calcium channels and calphostin C (0.5 μm) which selectively inhibits protein kinase C, all significantly inhibited maximum contractile responses of mesenteric arteries from control and diabetic rats to NaF. There were no significant differences between control and diabetic arteries in the relative magnitude of the inhibition produced by the three antagonists.
. These data suggest that there may be increased activation of the same signalling processes that mediate NA‐stimulated vasoconstriction, perhaps contraction‐associated G‐proteins or the effectors coupled to these G‐proteins, in response to NaF in mesenteric arteries from diabetic rats. This may also be responsible for the enhanced contractile responses of these arteries to α1‐adrenoceptor stimulation.
Spinal 5‐HT2 receptor‐mediated facilitation of pudendal nerve reflexes in the anaesthetized cat
Authors: Danuser Hansjorg , Thor Karl B. 
Published: July 2012

. 5‐Hydroxytryptamine (5‐HT) is intimately associated with central sympathetic and somatic control of the lower urinary tract. The sympathetic and somatic innervation of the lower urinary tract is conveyed through efferent axons of the hypogastric and pudendal nerves, respectively.
. The present study examined the effects of 2,5‐dimethoxy‐4‐iodophenylisopropylamine (DOI), a 5‐HT2 receptor subtype‐selective agonist, on evoked potentials recorded from the central ends of the hypogastric and pudendal nerves in response to electrical stimulation of afferent fibres in the pelvic and pudendal nerves, respectively. Various spinalization paradigms were employed to localize the site of action. All cats were pretreated with xylamidine (1 mg kg−1), a peripherally‐restricted 5‐HT2 receptor antagonist.
. In acute spinal cats, DOI (0.01–3 mg kg−1, i.v.) reliably produced dose‐dependent increases in the pudendal nerve reflex (to 228±31% of control). These increases were reversed by the 5‐HT2 receptor‐selective antagonist, LY53857 (0.3‐3 mg kg−1, i.v.). On the other hand, in spinally‐intact cats, DOI produced no significant changes in the pudendal reflex. However, within minutes of spinalization of DOI‐pretreated cats, a marked increase (to 221±16% of control) in the pudendal reflex was observed which could be reversed by LY53857. No significant effects were observed on hypogastric reflexes in either acute spinal or spinally‐intact cats following DOI administration. No effects were seen in either spinally‐intact or acute spinal animals when LY53857 was administered as the initial drug.
. These results indicate that activation of spinal 5‐HT2 receptors facilitates pudendal reflexes. In spinally‐intact cats, it is hypothesized that DOI activates supraspinal pathways that mediate inhibition of the pudendal reflexes and counteracts the facilitatory effects of spinal 5‐HT2 receptor activation.
Nitric oxide inhibition of basal and neurogenic mucus secretion in ferret trachea in vitro
Authors: Ramnarine S.I. , Khawaja A.M. , Barnes P.J. , Rogers D.F. 
Published: July 2012

In order to examine the role of nitric oxide (NO) on airway mucus secretion we studied the effects of the nitric oxide synthase (NOS) inhibitor l‐NG‐monomethyl‐l‐arginine (l‐NMMA), a novel nitric oxide donor, (±)‐(E)‐ethyl‐2‐[(E)‐hydroxyimino]‐5‐nitro‐3‐hexeneamide (FK409), and the NO precursor l‐arginine on basal mucus secretion in the ferret trachea in vitro in Ussing chambers. We also determined the effects of these agents upon secretion induced by electrical stimulation of nerves or by acetylcholine (ACh). We used 35SO4 as a mucus marker.
l‐NMMA (0.01‐1 mM) increased basal output of 35SO4‐labelled macromolecules with a maximal increase above baseline of 248% at 0.1 mM l‐NMMA. l‐Arginine (1 mM) alone had no significant effect on basal secretion but reversed the potentiating effect of l‐NMMA on basal secretion. l‐NMMA‐induced increases in basal mucus secretion were sustained for at least 30 min in the continuing presence of the NOS inhibitor. In contrast to the potentiating effects of l‐NMMA, FK409 (100 nM) reduced basal secretion by 60% (at 1 nM and at 10 nM it was without effect).
Electrical stimulation (50 V, 10 Hz, 0.5 ms for 5 min) increased 35SO4 output by 174%. l‐NMMA (1 and 10 mM) present during stimulation of tracheal segments resulted in significant potentiations of 214% and 116%, respectively, of the neurogenic response. The potentiated response to 10 mM l‐NMMA was reversed by l‐arginine (1 mM). At this dose l‐arginine had no effect itself on basal secretion. In contrast to the potentiating effects of l‐NMMA on neurogenic secretion, FK409 at 10 nM and 100 nM inhibited the neurogenic response by 98% and 99%.
At all concentrations tested, neither l‐NMMA (0.01 mM − 1 mM) nor FK409 (1 − 100 mM) had any significant effect on ACh‐induced mucus secretion.
These observations lead us to conclude that nitric oxide, derived from constitutive NO synthase, acts as an endogenous inhibitor of both basal and neurogenic mucus secretion in ferret trachea in vitro.