bluuebunny/crossref_metadata_2025_split huggingface dataset:
Release of vasopressin and oxytocin by excitatory amino acid agonists and the effect of antagonists on release by muscarine and hypertonic saline, in the rat in vivo
Authors: Bisset G.W. , Fairhall K.M. 
Published: July 2012

It has been claimed that glutamate is the dominant excitatory neurotransmitter in neuroendocrine regulation. The evidence is derived mainly from in vitro experiments.
We have investigated in vivo a possible role of excitatory amino acids (EAAs) in the neural control of release of vasopressin (AVP) and oxytocin from the neurohypophysis.
In rats under ethanol anaesthesia in which a diuresis was maintained by a constant fluid load, the i.c.v. injection of glutamate and the synthetic agonists α‐amino, 3‐hydroxy‐5‐methyl‐isoxazole‐4‐propionate (AMPA) and N‐methyl‐D‐aspartate (NMDA) produced an antidiuretic response (ADR) which was abolished by an AVP antagonist. For AMPA and NMDA it was shown that this ADR was accompanied by increased urinary excretion of AVP and oxytocin.
The selectivity of antagonists was tested in this system. D‐2‐Amino‐5‐phosphonopentanoate (D‐AP5) blocked the responses to NMDA but not to AMPA; 6‐cyano‐7‐nitroquinoxaline‐2, 3‐dione (CNQX) blocked the responses to both agonists.
The ADR to muscarine and hypertonic saline i.c.v., and the increase in excretion of AVP and oxytocin in response to muscarine, were blocked by CNQX but not by D‐AP5.
The results suggest that hypertonic saline releases AVP and muscarine releases both AVP and oxytocin, at least in part, by activating a glutaminergic input to the SON and PVN involving an AMPA receptor. This input could function as a terminal interneurone in afferent neural pathways to these nuclei.
Increase in insulin release from rat pancreatic islets by quinolone antibiotics
Authors: Maeda N. , Tamagawa T. , Niki I. , Miura H. , Ozawa K. , Watanabe G. , Nonogaki K. , Uemura K. , Iguchi A. 
Published: July 2012

The present study was undertaken to elucidate the mechanism(s) of hypoglycaemia caused by quinolone antibiotics. We investigated the effects of various quinolone antibiotics on insulin release in rat pancreatic islets.
At a non‐stimulatory concentration of 3 mM glucose, lomefloxacin (LFLX) or sparfloxacin at 1 mM and pipemidic acid (0.1‐1 mM) induced slight insulin release but tosufloxacin or enoxacin up to 100 μm did not.
At the stimulatory concentration of 10 mM glucose, all quinolones augmented insulin release in a dose‐dependent manner. LFLX (100 μm) shifted the dose‐response curve of glucose‐induced insulin release to the left without altering the maximal response.
At 10 mM glucose, LFLX (100 μm) increased insulin release augmented by forskolin (5 μm) or 12‐0‐tetradecanoyl phorbol‐13‐acetate (100 nM) but not by raising the K+ concentration from 6 to 25 mM.
Verapamil (50 μm) or diazoxide (50–400 μm) antagonized the insulinotropic effect of LFLX.
These data suggest that quinolone antibiotics may cause hypoglycaemia by increasing insulin release via blockade of ATP‐sensitive K+ channels.
Rise in cytosolic Ca2+ concentration induced by P2‐purinoceptor activation in isolated myocytes from the rat gastrointestinal tract
Authors: Blottière Hervé M. , Loirand Gervaise , Pacaud Pierre 
Published: July 2012

The changes in the free cytosolic Ca2+ concentration ([Ca2+]i) in response to agonists of P2‐purinoceptors were studied in myocytes isolated from the longitudinal muscle layer of different regions of the rat gastrointestinal tract (stomach, jejunum, ileum, caecum and colon). [Ca2+]i was estimated by emission from the fluorescent dye, indo‐1.
ATP and the P2Y‐purinoceptor agonist, 2‐methylthio‐ATP (2‐MeSATP), transiently increased [Ca2+]i in single myocytes from all segments of the gastrointestinal tract, whereas α,β‐methylene‐ATP, a P2X‐purinoceptor agonist, had no effect.
The rise in [Ca2+]i induced by ATP and 2‐MeSATP was maintained in Ca2+‐free solution but was abolished by depletion of the intracellular store with thapsigargin (1 μm).
Single myocytes from stomach, caecum and colon also responded to UTP by a transient increase in [Ca2+]i.
Individual myocytes responded to ATP, 2‐MeSATP and UTP in a nearly all‐or‐nothing manner. The increasing of agonist concentration enhanced the number of responding cells but did not increase the amplitude of the [Ca2+]i rise.
These results suggest that myocytes from the longitudinal layer of gastrointestinal muscle do not possess functional P2X‐purinoceptors and that agonists of P2Y and P2U‐purinoceptors induced a rise in [Ca2+]i, probably via an all‐or‐nothing mobilization of Ca2+ from intracellular stores.
Evidence for functional α2D‐adrenoceptors in the rat intestine
Authors: Liu Lu , Coupar Ian M. 
Published: July 2012

Peristaltic contractions were induced in segments of rat ileum by raising the intramural pressure. A mean pressure of 4.3±0.2 cmH20 (n = 112) was required to initiate rhythmic contractions of the longitudinal muscle (preparatory phase) and associated volume expulsions caused by circular muscle contraction. The frequency of peristalsis remained constant over two 15 min periods of stimulation.
The α2‐adreoceptor agonists, clonidine, UK 14,304, B‐HT 920, B‐HT 933 and the selective α2A‐ agonists, oxymetazoline and guanfacine, caused concentration‐dependent inhibition of peristaltic contractions. The potency order and IC50 values (nM) were: clonidine (2.81)≥oxymetazoline (4.23) ≥ UK 14,304 (4.48) ≥ guanfacine (5.51) > B‐HT 920 (78.72) > B‐HT 933 (442.48).
High concentrations of clonidine, amounting to more than 10 and 100 times the IC50 value in the peristaltic reflex (30 and 300 nM respectively), failed to inhibit the cholinergic contractile response to transmural electrical stimulation over the range of 2.5 to 40 Hz.
α2‐Adrenoceptor antagonists were used to determine the subtype of presynaptic α2‐adrenoceptor in rat ileum. All the antagonists tested caused parallel shifts to the right of the concentration‐response regression line to clonidine and none, except ARC 239, influenced the rate of peristalsis. However, ARC 239 significantly decreased the frequency of control period peristaltic contractions. The order of affinity of the antagonists against clonidine (pKB values in parentheses) was RX 821002 (8.99) > phentolamine (8.07) > BRL 44408 (7.43) ≥ rauwolscine (7.41) ≥ yohimbine (7.28) > prazosin (5.86) ≥ ARC 239 (5.74).
These results, when compared with binding and functional data from various other tissues and cell lines, are consistent with the presence of presynaptic α2D‐adrenoceptors in rat ileum. Further evidence is provided that this subtype of α2‐adrenoceptor is probably located proximal to the final cholinergic neurones in the reflex arc.
Oxytocin receptors expressed and coupled to Ca2+ signalling in a human vascular smooth muscle cell line
Authors: Yazawa Hidenori , Hirasawa Akira , Horie Kuniko , Saita Yuji , Iida Emi , Honda Kazuo , Tsujimoto Gozoh 
Published: July 2012

In a human vascular smooth muscle cell line (HVSMC), binding experiments with [3H]‐arginine8‐vasopressin (AVP) have shown the existence of a homogeneous population of binding sites with affinity (Kd value) of 0.65 nM and a maximum number of binding sites (Bmax) of 122 fmol mg−1 protein.
Nonlabelled compounds compete for [3H]‐AVP binding in the HVSMC membrane with an order of potency of oxytocin > lyspressin ≥ AVP > Thr4, Gly7‐oxytocin > (β‐mercapto‐β‐β‐cyclopentamethylenepropionyl‐O‐Me Tyr2, Arg8) vasopressin > desmopressin > OPC21268 > OPC31260. This order was markedly different from that observed in rat vascular smooth muscle cells (A10), a well‐established V1A receptor system.
In HVSMC both oxytocin and AVP increased inositol 1,4,5‐trisphosphate (IP3) production and [Ca2+]i response, but the efficacy of the responses was greater for oxytocin than AVP.
Reverse transcription‐polymerase chain reaction (RT‐PCR) assay detected only oxytocin receptor but not V1A or V2 receptors in HVSMC, whereas only V1A receptors were found in A10 cells.
In conclusion, in HVSMC only oxytocin receptors are expressed among the vasopressin receptor family, and they coupled to phosphatidyl inositol (PI) turnover/Ca2+ signalling. This unexpected observation should provide new insight into the functional role of the oxytocin receptor in a human vascular smooth muscle cell line.
Suppression of reperfusion‐induced arrhythmias with combined administration of 5‐HT2 and thromboxane A2 antagonists
Authors: Shaw Linda A. , Coker Susan J. 
Published: July 2012

The effects of the 5‐HT2 antagonist, ICI 170,809 and the thromboxane A2 antagonist, ICI 192,605, given alone and in combination (n = 12 per group), were examined in anaesthetized rats. Haemodynamics and arrhythmias induced by permanent coronary artery occlusion or by reperfusion after 5 min of ischaemia were monitored.
In a study on reperfusion‐induced arrhythmias, the only significant effect of ICI 170,809 (1 mg kg−1, i.v.) was a reduction in the number of ventricular premature beats (VPBs). ICI 192,605 (1 mg kg−1 min−1, i.v.) did not alter reperfusion‐induced arrhythmias. However, in combination, when compared with controls, these drugs caused significant reductions in the incidence of ventricular tachycardia (VT), 100% to 58%; ventricular fibrillation (VF), 92% to 33%; and the mortality due to sustained VF, 67% to 17%. There was also a significant reduction in the number of VPBs following reperfusion.
In a second study with lower doses of drugs, ICI 170,809 (0.3 mg kg−1) and ICI 192,605 (0.3 mg kg−1 min−1) had no significant effects on reperfusion‐induced arrhythmias either alone or in combination.
A third study examined the effects of the higher doses of the drugs on ischaemia‐induced arrhythmias. Neither drug alone, nor in combination, altered the incidence of ischaemia‐induced VT, VF, the mortality, or the number of VPBs.
These results indicate that, in contrast to the administration of either drug alone, combined administration of a 5‐HT2 antagonist and a thromboxane A2 antagonist caused marked suppression of reperfusion‐induced but not ischaemia‐induced arrhythmias.
Different pharmacological characteristics in L6 and C2C12 muscle cells and intact rat skeletal muscle for amylin, CGRP and calcitonin
Authors: Pittner Richard A. , Wolfe‐Lopez Deborah , Young Andrew A. , Beaumont Kevin 
Published: July 2012

We compared the ability of rat amylin, rat calcitonin gene‐related peptide (CGRP) and rat and salmon calcitonins to elevate cyclic AMP levels and to inhibit [U‐14C]‐glucose incorporation into glycogen in insulin‐stimulated intact rat soleus muscle and in two cell lines derived from rodent skeletal muscle, L6 and C2C12
In intact soleus muscle, both amylin (EC50s of 0.7‐6.1 nM) and salmon calcitonin (EC50s of 0.5‐1.4 nM) were more potent than CGRP (EC50s of 5.6–15.8 nM) and were much more potent than rat calcitonin (EC50s of 50–137 nM) at stimulating cyclic AMP production, activating glycogen phosphorylase and inhibiting insulin‐stimulated [14C]‐glycogen formation.
In contrast, in both L6 and C2C12 cells, CGRP (EC50s of 0.042‐0.12 nM) stimulated cyclic AMP formation and inhibited insulin‐stimulated [U‐14C]‐glucose incorporation into glycogen approximately 1000 times more potently than amylin (EC50s 34–240 nM), while salmon calcitonin was without measurable effect.
There was a correlation between elevation of cyclic AMP and inhibition of insulin‐stimulated [U‐14C]‐glucose incorporation into glycogen evoked by these peptides in both intact muscle (r2 = 0.69, P <0.0004) and muslce cell lines (r2 = 0.96, P <0.0001).
In conclusion, the effects of amylin, CGRP, and calcitonin on soleus muscle glycogen metabolism appear to be mediated by adenylyl cyclase‐coupled receptors which show a pharmacological profile similar to high affinity amylin binding sites that have been previously reported in rat brain. In contrast, the effects of amylin and CGRP in L6 and C2C12 rodent muscle cell lines appear to be mediated by adenylyl cyclase‐coupled receptors that behave like CGRP receptors.
Modulation of vasorelaxant responses to potassium channel openers by basal nitric oxide in the rat isolated superior mesenteric arterial bed
Authors: McCulloch Audrey I. , Randall Michael D. 
Published: July 2012

We have used the isolated buffer‐perfused mesenteric arterial bed of the rat to assess the modulation of vasorelaxation to potassium channel openers (KCOs) by basal nitric oxide.
The dose‐response curves to the KCOs, levcromakalim and pinacidil, in preconstricted preparations were significantly shifted to the left in the presence of the nitric oxide synthase inhibitor (100 μm) NG‐nitro‐L‐arginine methyl ester (levcromakalim, ED50=4.47±0.70 nmol vs. 1.73±0.26 nmol, P<0.001; pinacidil, ED50=16.1±4.8 nmol vs. 5.43±1.10 nmol, P<0.001). The vasorelaxant responses to papaverine, a vasodilator which acts independently of potassium channels was unaffected by NG‐nitro‐L‐arginine methyl ester (L‐NAME).
Removal of the endothelium, by perfusion with the detergent CHAPS (0.3%), significantly (P<0.001) increased the potency of levcromakalim as a vasodilator (ED50 4.47±0.70 nmol vs. 2.59±0.31 nmol). The subsequent administration of L‐NAME following perfusion with CHAPS did not lead to any additional enhancement of responses to levcromakalim.
The presence of the non‐selective adenosine antagonist, 8‐phenyltheophylline (8‐PT, 10 μm) significantly (P<0.001) shifted the dose‐response curve to levcromakalim to the left (ED50 4.47±0.70 nmol vs. 1.11±0.32 nmol). In the presence of both L‐NAME and 8‐PT, the dose‐response curve to levcromakalim was also significantly (P<0.01) shifted to the left compared with control (ED50 in the presence of both L‐NAME and 8‐PT was 0.42±0.08 nmol).
The presence of 8‐bromo cyclic GMP (10 μm) reversed the increase potency of levcromakalim, observed following inhibition of nitric oxide synthase (ED50 in the presence of L‐NAME was 0.59±0.01 nmol and in the presence of 8‐bromo cyclic GMP plus L‐NAME the ED50 was 3.17±0.80 nmol). However in the absence of L‐NAME, the cell permeable analogue of cyclic GMP, 8‐bromo cyclic GMP, did not affect the dose‐response curve to levcromakalim compared with control (control ED50 value was 4.16±0.52 nmol vs. 3.85±1.13 nmol in the presence of 8‐bromo cyclic GMP).
The present investigation demonstrates that both basal nitric oxide and adenosine modulate vasorelaxation to the KCOs levcromakalim and pinacidil. The modulatory effect of nitric oxide may be mediated via cyclic GMP.
Enhancement of sympathetic purinergic neurotransmission in the guinea‐pig isolated vas deferens by the novel ecto‐ATPase inhibitor ARL 67156
Authors: Westfall T.D. , Kennedy C. , Sneddon P. 
Published: July 2012

Field stimulation of the sympathetic nerves of the guinea‐pig isolated vas deferens with trains of pulses for 20 s at 1–8 Hz produced characteristic biphasic contractions. The effect of the novel ecto‐ATPase inhibitor, 6‐N,N‐diethyl‐D‐β,γ‐dibromomethyleneATP (ARL 67156, formerly known as FPL 67156), on the magnitude of the initial, predominantly purinergic peak of this response was studied in order to determine the influence of enzymatic degradation of adenosine 5′‐triphosphate (ATP) on its action as a neurotransmitter.
The peak magnitude of the response to nerve stimulation was significantly increased in a concentration‐dependent manner by ARL 67156 (5–100 μm) and the size of the neurogenic response at 4 Hz was approximately doubled in the presence of ARL 67156 (100 μm).
ARL 67156 (100 μm) has a rapid onset of action. The enhancing effect on neurogenic contractions was maximal after 10 min, was well maintained for at least 30 min and was rapidly reversed, with responses returning to control levels 10 min after washout.
The neurogenic contraction in the presence of prazosin (0.1 μm) was purely purinergic, as it was abolished by the P2‐purinoceptor antagonist, PPADS (100 μm). ARL 67156 (100 μm) produced a similar degree of enhancement of neurogenic responses in the absence and presence of prazosin, supporting the view that the enhancing effects of ARL 67156 on neurogenic contractions result from potentiation of the action of ATP.
Exogenous ATP and α,β‐methyleneATP produced rapid transient contractions. Responses to ATP were increased in magnitude and duration in the presence of ARL 67156 (100 μm), whereas those to the stable analogue, α,β‐methyleneATP were not significantly affected.
Contractions to exogenous noradrenaline (10 μm) and KCl (40 mM) were significantly enhanced by ARL 67156 (100 μm), but this potentiation was abolished by PPADS (100 μm). Therefore, this effect of the ecto‐ATPase inhibitor may be due to a build up of endogenous ATP, increasing the sensitivity of the smooth muscle to other agonists.
It is concluded that ARL 67156 potentiates the action of ATP, and that when ATP acts as a neurotransmitter its postjunctional actions are greatly attenuated by enzymatic degradation.
Modulation by nitric oxide and prostaglandin of the renal vascular response to angiotensin II (3–8)
Authors: Yoshida Makoto , Kikukawa Masanobu , Hisa Hiroaki , Satoh Susumu 
Published: July 2012

The aim of this study was to investigate the renal vascular response to angiotensin II (3–8) (AIV). The effect of the nitric oxide synthase inhibitor, NG‐nitro‐L‐arginine methyl ester (L‐NAME) or the cyclo‐oxygenase inhibitor, indomethacin on the AIV‐induced response was examined in anaesthetized spontaneously hypertensive rats (SHR) and normotensive Wistar‐Kyoto rats (WKY).
Intrarenal infusion of AIV produced a biphasic vasoconstrictor response. The vasoconstriction developed rapidly to reach a maximum followed by a partial recovery to a sustained lesser level of vasoconstriction. The initial maximum response was enhanced by L‐NAME but not affected by indomethacin treatment. The simultaneous administration of L‐NAME and indomethacin prevented the partial recovery resulting in a greater sustained level of constriction.
A stable vasoconstriction of relatively constant magnitude was observed with angiotensin II (AII) infusion. The AII vasoconstriction was enhanced by L‐NAME but not changed by indomethacin. The combination of these inhibitors further enhanced the AII‐induced vasoconstriction in WKY, but not in SHR.
Pretreatment with the AII receptor antagonist, losartan, inhibited the vasoconstriction induced by AIV and AII.
These results suggest that nitric oxide and prostaglandins may modulate the renal vascular response to AIV.
In situ assessment of the role of the β1, β2‐ and β3‐adrenoceptors in the control of lipolysis and nutritive blood flow in human subcutaneous adipose tissue
Authors: Barbe Pierre , Millet Laurence , Galitzky Jean , Lafontan Max , Berlan Michel 
Published: July 2012

The involvment of β1, β2‐ and β3‐adrenoceptors in the control of lipolysis and nutritive blood flow was investigated in abdominal subcutaneous adipose tissue of healthy young adults by use of an in situ microdialysis technique.
Dialysis probes were infused either with isoprenaline (non‐selective β‐adrenoceptor agonist), CGP 12,177 (selective β3‐adrenoceptor agonist having β1‐/β2‐antagonist properties), dobutamine (selective β1‐adrenoceptor agonist) or terbutaline (selective β2‐adrenoceptor agonist). The recovery of each probe used for perfusion was calculated by an in vivo calibration method. The local blood flow was estimated through the measurement of the escape of ethanol infused simultaneously with the drugs included in the probe.
Isoprenaline infusion at 0.01 μm had a weak effect while higher concentrations of isoprenaline (0.1 and 1 μm) caused a rapid, sustained and concentration‐dependent increase of glycerol outflow; the maximum increase was 306±34% with 1 μm. Isoprenaline also increased the nutritive blood flow in adipose tissue; a significant effect appeared at 0.1 μm isoprenaline and was greater at 1 μm.
CGP 12,177 (10 and 100 μm) increased the glycerol concentration in the dialysate (128±8 and 149±12%, respectively) and nutritive blood flow. Terbutaline and dobutamine (100 μm) both provoked rapid and similar increases in glycerol outflow (252±18 and 249±18%, respectively). Both, terbutaline and dobutamine increased nutritive blood flow.
It is concluded that β1 and β2‐adrenoceptor subtypes are both mainly involved in the mobilization of lipids and in the control of nutritive blood flow. β3‐Adrenoceptors play a weaker role in the control of lipolysis and nutritive blood flow in human subcutaneous abdominal adipose tissue.
Angiotensin II‐elicited signal transduction via AT1 receptors in endothelial cells
Authors: Pueyo Maria E. , N'Diaye Nina , Michel Jean‐Baptiste 
Published: July 2012

. Angiotensin II (AII) actions are mediated by two distinct types of receptors: AT1, which includes two subtypes, AT1A and AT1B, and AT2. AII produces vasoconstriction on the vascular wall acting directly on smooth muscle cells via AT1 receptors. AII receptors have recently been demonstrated on endothelial cells. But the pharmacological characteristics of these receptors and the intracellular signal pathways coupled to them remain unclear.
. The aim of this work was to characterize the AII receptor subtypes in rat aortic endothelial cells (RAEC) in primary culture and to evaluate the signal pathways coupled to these receptors by measuring the activation of phospholipase C (PLC) and phospholipase A2 (PLA2).
. Labelled AII bound to RAEC in a specific, saturable manner. Scatchard analysis showed a Kd of 1.87±0.49 nM and a Bmax of 50.2±10.9 × 103 sites per cell. AII was displaced by the AT1‐specific antagonist, DuP753 with a Ki of 17.37 ± 1.49 nM, but not by the AT2 receptor analogues CGP42771B or PD123177. These data were confirmed by the finding of AT1 mRNA in endothelial cells. Analysis of RNA expression by RT‐PCR showed the presence of both subtypes, AT1A and AT1B, in endothelial cells, whereas smooth muscle cells express only AT1A.
. The activation of PLC and PLA2 in response to AII was evaluated by measuring inositol phosphate production and arachidonic acid release, respectively. Both were enhanced by AII in a dose‐dependent manner, and inhibited by DuP753, but not by PD123177.
. We conclude that AT1 receptors are expressed by endothelial cells in primary culture and that phospholipase C and phospholipase A2 are activated via this receptor.