bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanism of action of α‐adrenoceptor activation in single cells freshly dissociated from the rabbit portal vein
Authors: Byrne N.G. , Large W.A. 
Published: July 2012

The action of noradrenaline was studied in freshly dispersed cells of the rabbit portal vein using microelectrode techniques.
In normal physiological salt solution, the ionophoretic application of noradrenaline evoked an α‐adrenoceptor‐mediated depolarization and sometimes a β‐adrenoceptor‐mediated hyperpolarization. Experiments were carried out in the presence of propranolol to study the membrane mechanism associated with α‐adrenoceptor activation.
In the current clamp mode of recording, the equilibrium potential of the noradrenaline‐evoked depolarization was −1.9 mV. The depolarization was brought about by an increase in membrane conductance.
Under voltage clamp conditions, noradrenaline produced an inward current with a reversal potential of −7 ± 3 mV (mean ± s.e. mean).
The relationship between the noradrenaline‐induced inward current and clamp potential was non‐linear. Depolarization enhanced the conductance elicited by noradrenaline.
Evidence is presented which suggests that an additional conductance mechanism (probably an increase in potassium conductance) is also evoked by α‐adrenoceptor stimulation in dispersed cells of rabbit portal vein.
Influence of halothane on electrical coupling in cell pairs isolated from guinea‐pig ventricle
Authors: Terrar D.A. , Victory J.G.G. 
Published: July 2012

The actions of halothane on electrical coupling between cells were investigated in cell pairs isolated from guinea‐pig ventricular muscle.
Under voltage‐clamp conditions a step depolarization applied to one cell caused a similar change in potential in the second. Application of halothane led to the appearance of double peaks in inward current evoked by step depolarizations. These observations were interpreted in terms of uncoupling of the cells leading to escape of the second cell from the influence of the voltage‐clamp in the first cell.
This suggestion that uncoupling in the presence of halothane led to differences in electrical activity in the two cells was confirmed in experiments in which independent electrodes were used to measure membrane potential in the two cells.
The voltage responses of both cells of the pair were recorded in response to constant current pulses. Administration of halothane led to abolition of the response recorded from the second cell while that of the first was enhanced. The actions are consistent with an action of halothane on gap junctions to block electrical coupling.
Qualitatively similar observations, consistent with electrical uncoupling, were observed with isoflurane.
These findings may be significant in relation to the arrhythmogenic actions of halothane.
Calcium and the activation of the α1‐adrenoceptors in the guinea‐pig taenia caeci
Authors: Rusko J. , Bauer V. 
Published: July 2012

The actions of phenylephrine (0.1–100 μmol l−1) and methoxamine (0.1–100 μmol l−1) were compared with that of adrenaline (0.01–10 μmol l−1) using the single sucrose gap method and mechanical recording in the guinea‐pig taenia caeci. Drugs were applied for variable periods of time.
The characteristics of the inhibitory effects of α‐adrenoceptor agonists were the same when exposure time did not exceed 5 min. When the exposure was prolonged, in contrast to the sustained effects of adrenaline (0.1–3 μmol l−1), phenylephrine and methoxamine (1–10 μmol l−1) produced a transient inhibitory action.
During the delayed recovery phase of phenylephrine, adrenaline preserved its ability to suppress the spontaneous electrical and mechanical activities of the taenia both when phenylephrine was replaced by adrenaline or when adrenaline was applied in addition to phenylephrine. All the above effects were found in untreated preparations, as well as during blockade of muscarinic cholinoceptors by atropine (1.4 μmol 1−1), β‐adrenoceptors by propranolol (3 μmol l−1) and release of endogenous catecholamines by guanethidine (2.5μmol l−1).
In the presence of phorbol 12,13‐dibutyrate adrenaline ceased to be effective, while the inhibitory action of phenylephrine was converted to a contraction.
In calcium‐free conditions in the presence of EGTA (0.4 mmol l−1) the initial hyperpolarization induced by adrenaline and phenylephrine was significantly reduced and with repeated applications of the agonists the inhibitory response disappeared. Similar results were obtained using tissues treated with nifedipine (1 and 10 μmol l−1). When caffeine (30 mmol l−1) was present in the calcium‐free solution the α‐agonists studied were unable to produce any membrane potential changes.
The present results imply that the inhibitory effect of α1‐adrenoceptor agonists is mediated by the opening of potassium channels, which are activated by calcium derived from an intercellular source supplied from the extracellular space via a nifedipine‐sensitive mechanism.
Inhibitory effects of procaine on contraction and calcium movement in vascular and intestinal smooth muscles
Authors: Ahn H.Y. , Karaki H. 
Published: July 2012

The effects of procaine on muscle tension and 45Ca2+ movements were investigated in vascular smooth muscle of the rabbit aorta and intestinal smooth muscle of the taenia isolated from guinea‐pig caecum.
Procaine (10 mm) induced a contraction in the taenia but had little effect on the resting tension in the aorta.
Procaine, 0.5–10 mM, relaxed the sustained contractions induced by 65.4 mM KCl and 10−6 m noradrenaline in the aorta, and by 45.4 mM KCl, 10−6 m carbachol and 10−6 m histamine in the taenia. The inhibitory effect of procaine on the high K+‐induced contractions was antagonized by external Ca2+ but not by the Ca2+ channel activators, Bay K 8644 and CGP 28,392.
45Ca2+ uptake was increased by high K+ or noradrenaline in the aorta and by high K+ or carbachol in the taenia. The increments were inhibited by procaine at the concentrations needed to inhibit the muscle contractions.
In a Ca2+‐free solution, noradrenaline and caffeine induced a transient contraction in the aorta, whereas a second application of each stimulant was almost ineffective. Addition of 1–10 mM procaine shortly before the first application of the stimulant inhibited the contraction. After washing the muscle with a Ca2+‐free solution without procaine, the second application of the stimulant induced a greater contraction than that in control muscle without procaine pretreatment.
Noradrenaline and caffeine released 45Ca2+ from a cellular site in the aorta. Procaine inhibited the effects of these stimulants.
It was concluded that procaine may inhibit both the opening of Ca2+ channels and the release of Ca2+ from cellular stores and the former but not the latter effect may be attributable to a local anaesthetic action.
α‐Methyldopa produces mydriasis in the rat by stimulation of CNS α2‐adrenoceptors
Authors: Hey John A. , Ito Takashi , Koss Michael C. 
Published: July 2012

The effects of i.v. administration of α‐methyldopa (MD) on rat pupil diameter were investigated. All experiments were carried out in rats in which vagosympathetic nerve trunks were sectioned bilaterally at the cervical level.
In anaesthetized rats MD produced a marked dose‐related increase in pupil diameter. The onset of pupillary response to MD was gradual and reached maximal levels 2–3 h after administration.
Pretreatment with α2‐adrenoceptor antagonists yohimbine (1.5 mg kg−1, i.v.) or idazoxan (0.5 mg kg−1, i.v.) blocked the pupillary response to MD. In contrast, the α1‐antagonists prazosin (1.0 mg kg−1, i.v.) and phenoxybenzamine (1.5 mg kg−1, i.v.) did not significantly alter the pupillary effects of MD.
Selective enzymatic blockade with 3‐hydroxy‐benzyl‐hydrazine (NSD‐1015; 25 mg kg−1, i.p.), a dopa‐decarboxylase inhibitor, as well as bis (4‐methyl‐homopiperazinyl‐thiocarbonyl) disulphide (FLA‐63, 5.0 mg kg−1, i.p.), a dopamine‐β‐hydroxylase inhibitor, prevented the mydriatic effect of MD.
The above findings support the hypothesis that MD produces a clonidine‐like CNS mydriasis in the rat. This effect appears to be mediated primarily by the MD metabolite, α‐methylnoradrenaline.
These results indicate that MD produces mydriasis in the rat by a CNS action. The mydriatic action of MD appears to be produced by its metabolite α‐methylnoradrenaline which in turn stimulates CNS postsynaptic α2‐adrenoceptors.
Effects of anterior hypothalamic lesions and sham‐operations on bacterial endotoxin‐induced non‐specific airway hyperreactivity in vivo and in vitro
Authors: Van Oosterhout Antoon J.M. , Woutersen‐van Nijnanten Felice M.A. , Folkerts Gert , Nijkamp Frans P. 
Published: July 2012

In the present study the effects of anterior hypothalamic (AHA) lesions and sham‐operations were investigated on the endotoxin‐induced airway hyperreactivity in guinea‐pigs. Unoperated, sham‐operated and AHA‐lesioned guinea‐pigs were injected intraperitoneally with Escherichia coli endotoxin and the airway reactivity tested four days later in isolated tracheal spirals and in spontaneously breathing anaesthetized animals. Control animals were given sterile saline.
Sham‐operated control animals demonstrated a diminished responsiveness of the tracheal spirals in vitro and of the lung resistance (ΔR1) in vivo to histamine receptor and cholinoceptor‐muscarinic agonists as compared to unoperated control animals.
AHA‐lesioned control animals showed a responsiveness of the respiratory airways in vitro and in vivo between the values of unoperated and sham‐operated control animals, suggesting that lesions partially restored the diminished responsiveness.
In unoperated and sham‐operated guinea‐pigs, endotoxin administration induced hyperreactivity of the tracheal spirals and ΔR1 to histamine receptor and cholinoceptor‐muscarinic agonists with respect to the control groups.
In AHA‐lesioned animals, the endotoxin‐induced airway hyperreactivity in vitro and in vivo to histamine receptor and cholinoceptor‐muscarinic agonists was absent.
Contribution of galanin to non‐cholinergic, non‐adrenergic transmission in rat ileum
Authors: Muramatsu Ikunobu , Yanaihara Noboru 
Published: July 2012

We examined the possibility that the neuropeptide, galanin, may act as a transmitter in longitudinal muscle isolated from the rat ileum.
Galanin at nanomolar concentrations produced a phasic contraction with a concomitant increase in rhythmic activity. At concentrations in excess of 3 × 10−8 m, the contraction was followed by a rapid desensitization; hence, with the cumulative re‐addition of galanin, there was no response. This desensitization was probably selective for galanin because there was no attenuation of the contractile responses to substance P, neurokinin A and B, bradykinin or carbachol.
The phasic contraction induced by galanin was not inhibited by atropine, guanethidine, hexamethonium, naloxone, tetrodotoxin or [D‐Pro2, D‐Trp7,9]‐substance P.
Electrical stimulation of intramural nerves at low frequencies (1–5 Hz) led to an augmentation of spontaneous rhythmic contractions, which were completely or partially inhibited by atropine. However, guanethidine, hexamethonium, naloxone, [D‐Pro2, D‐Trp7,9]‐substance P and desensitization to galanin were without effect on the response to such electrical stimulation.
In contrast, transmural electrical stimulation at higher frequencies in the presence of atropine and guanethidine produced biphasic contractile responses with transient and slow components. The slow component was selectively attenuated by galanin desensitization.
The slow component induced by high frequency stimulation was markedly attenuated by repeated electrical stimulation at short intervals (2.5 min between 30 s trains). Following repeated stimulation, the contractile response to galanin was also attenuated. Thus, a cross‐desensitization between the mediator of the slow component and galanin had to be considered. In contrast, responses to tachykinins and the transient component induced by electrical stimulation were without effect.
Somatostatin, vasoactive intestinal polypeptide and α,β‐methylene ATP were without effect on the tone of the muscle. Calcitonin gene‐related peptide, neurotensin, gastrin‐releasing peptide, neuropeptide Y and capsaicin produced either a transient arrest of the spontaneous rhythmic activity or a transient relaxation.
These results suggest that the slow component of the non‐cholinergic non‐adrenergic contraction, as induced by intramural nerve stimulation is apparently due to the endogenous release of galanin, presumably released from galanin‐containing nerves in the rat ileum.
Facilitation of noradrenaline release from sympathetic nerves in rat anococcygeus muscle by activation of prejunctional β‐adrenoceptors and angiotensin receptors
Authors: Li Chunguang , Majewski Henryk , Rand Michael J. 
Published: July 2012

Isolated preparations of rat anococcygeus muscle were incubated with [3H]‐noradrenaline and the efflux of radioactivity induced by stimulation of intramural sympathetic nerves was used as a measure of release of transmitter noradrenaline. Isometric contractile responses were also measured.
Angiotensin I (0.03 μm) and angiotensin II (0.03 μm) produced non‐sustained contractile responses and enhanced the stimulation‐induced (S‐I) effluxes of radioactivity as well as the contractile responses to electrical stimulation. These effects were blocked by the angiotensin II receptor antagonist saralasin (0.03 μm), and the effect of angiotensin I, but not angiotensin II, was blocked by the angiotensin converting enzyme inhibitor captopril (0.1 μm).
The findings indicate that there are both pre‐ and postjunctional receptors for angiotensin II and that angiotensin I is converted to angiotensin II in the anococcygeus muscle preparation.
Isoprenaline (0.1 μm) slightly enhanced the S‐I efflux of radioactivity, and produced a greater enhancement after neuronal uptake blockade with desipramine (0.03 μm) and α‐adrenoceptor blockade with phentolamine (1 μm).
The facilitatory effect of isoprenaline on S‐I efflux of radioactivity was abolished by propranolol (0.3 μm), but was not affected by low concentrations of saralasin (0.03 μm) or captopril (0.1 μm) which abolished the effect of angiotensin I. The findings suggest that isoprenaline acts directly on prejunctional β‐adrenoceptors to enhance S‐I noradrenaline release, rather than indirectly by releasing angiotensin II from within the tissue. Higher concentrations of saralasin (0.1 μm) or captopril (5 μm) did block the facilitatory effect of isoprenaline. The significance of this finding is not clear.
Effects of 5‐hydroxytryptamine agonists and antagonists on the responses of rat spinal motoneurones to raphe obscurus stimulation
Authors: Roberts M.H.T. , Davies M. , Girdlestone D. , Foster G.A. 
Published: July 2012

The excitability of lumbar spinal motoneurones was studied in halothane‐anaesthetized rats by recording with microelectrodes the amplitude of the population spike evoked antidromically by stimulation of the cut ventral roots.
Electrical stimulation of the nucleus raphe obscurus for 1 min at 20 Hz increased the population spike amplitude and, as shown by intracellular recording, depolarized motoneurones. This response could be mimicked by microinjection of dl‐homocysteic acid into raphe obscurus but the response was not present in animals pretreated wtih the 5‐hydroxytryptamine (5‐HT) neurotoxin 5,7‐dihydroxytryptamine (5,7‐DHT).
Microiontophoretically applied 5‐HT had very similar effects on the extracellularly recorded population spike to those caused by stimulation of the raphe obscurus. These responses to 5‐HT were larger in 5,7‐DHT‐pretreated animals.
The effects of 5‐HT were potently mimicked by iontophoretically applied 5‐carboxamidotryptamine but 8‐hydroxy‐2‐(di‐n‐propylamino) tetralin (8‐OH‐DPAT) was without effect.
Antagonists were applied by microiontophoresis and also by intravenous injection. Ketanserin, the selective 5‐HT2 antagonist, did not antagonize the effects of 5‐HT. Neither did the 5‐HT3‐receptor antagonist MDL 72222 or the selective 5‐HT1 binding ligand cyanopindolol.
The non‐selective 5‐HT1/5‐HT2‐receptor antagonist methysergide was an effective antagonist of both the effects of 5‐HT and the response to raphe obscurus stimulation. Methysergide did not reduce the excitatory effects of noradrenaline.
It is concluded that 5‐HT application and stimulation of raphe obscurus increase the excitability of motoneurones by an action on a 5‐HT1‐like receptor which appears to be different from the 5‐HT1A‐and the 5‐HT1B‐binding sites characterized by others.
Endothelium‐derived relaxing factor and the effects of acetylcholine and histamine on resistance blood vessels
Authors: Bhardwaj R. , Moore P.K. 
Published: July 2012

The role of endothelium‐derived relaxing factor (EDRF) in the action of vasodilator (acetylcholine, histamine, nitroprusside) and vasoconstrictor (noradrenaline, vasopressin) drugs on vascular resistance in the isolated perfused kidney and mesentery of the rat was studied.
Acetylcholine (EC50 = 0.18 ± 0.05 nmol and 3.1 ± 0.06 nmol, n = 8) and histamine (EC50 = 31.2 ± 4.9 nmol and 46.2 ± 3.9 nmol, n = 8) produced dose‐related vasodilatation in noradrenaline‐preconstricted (i.e. ‘high tone’) rat renal and mesenteric blood vessels. The response to both vasodilators (but not nitroprusside) was abolished by infusion of CHAPS (4.7 mg ml−1, 30 s). By use of an immunocytochemical staining procedure CHAPS was demonstrated to remove vascular endothelial cells lining intrarenal blood vessels.
Gossypol (3 μm), metyrapone (10 μm) and nordihydroguaiaretic acid, (NDGA, 30 μm), presumed inhibitors of EDRF biosynthesis, reduced or abolished the response to acetylcholine and histamine in perfused kidney and mesentery of the rat without affecting vasodilatation due to nitroprusside. Mepacrine (10 μm) similarly abolished the response to acetylcholine and histamine but in addition, reduced the response to nitroprusside in both preparations.
Methylene blue (100 μm), a presumed antagonist of the effect of EDRF, abolished vasodilatation due to acetylcholine and histamine and reduced the response to nitroprusside in perfused rat kidney and mesentery. Superoxide dismutase, SOD (15 u ml−1), was without effect.
While CHAPS treatment significantly augmented the vasoconstrictor response to both noradrenaline and vasopressin in perfused renal and mesenteric vessels this effect was not mimicked by metyrapone or gossypol suggesting that the enhanced effect of vasopressor agents in CHAPS‐perfused rat organs is due to the removal of a permeability barrier rather than impaired EDRF formation.
Responses to vasoconstrictor and vasodilator drugs in the perfused kidney and mesentery were obtained in the presence of indomethacin (8/XM) which produced in excess of 90% inhibition of prostacyclin (PGI2) release as measured by radioimmunoassay of 6‐oxo‐prostaglandin F1α (6‐oxo‐PGF1α) in the Krebs effluent.
We provide evidence that EDRF mediates the vasodilator response to acetylcholine and histamine in resistance blood vessels in perfused rat kidney and mesentery. The possibility that EDRF has a physiological role to play in regulating the calibre of resistance blood vessels is discussed.
Agonists at μ‐opioid, M2 ‐muscarinic and GABAB ‐receptors increase the same potassium conductance in rat lateral parabrachial neurones
Authors: Christie M.J. , North R.A. 
Published: July 2012

Intracellular recordings of membrane potential and current were made from neurones in the lateral parabrachial nucleus in slices of rat brain in vitro.
The membrane was hyperpolarized by the opioid peptides Tyr‐d‐Ala‐Gly‐MePhe‐Gly‐ol (DAGOL, 0.01–1μm) and [Met5]enkephalin (3–30μm), though not by Tyr‐d‐Pen‐Gly‐Phe‐d‐Pen and U50488. In two experiments, naloxone competitively antagonized the effects of DAGOL and [Met]enkephalin with equilibrium dissociation constants of 0.8 and 3.2 nM, respectively.
Baclofen (0.3–30 μm) also hyperpolarized the neurones; this action was unaffected by naloxone.
DAGOL, [Met5]enkephalin and baclofen caused outward currents at the resting potential. These currents reversed polarity at a membrane potential which changed with the logarithm of the extracellular potassium concentration.
Muscarine has been shown previously to increase the potassium conductance by an action at M2‐receptors: the potassium currents induced by maximal concentrations of muscarine, baclofen and [Met5]enkephalin were non‐additive, indicating that these agonists opened the same population of potassium channels.
Noradrenaline, UK14304, carboxamidotryptamine, dopamine, adenosine and somatostatin had little or no effect on membrane potential.
It is concluded that rat lateral parabrachial neurones express μ‐opioid, γ‐aminobutyric acidB (GABAB), and M2‐muscarinic receptors: activation of any of these receptors increases the potassium conductance of the membrane and inhibits the neurones through hyperpolarization.
The effects of endothelium‐dependent vasodilators on cardiac output and their distribution in the anaesthetized rat: a comparison with sodium nitroprusside
Authors: Thomas G. Roger , Thiemermann Christoph , Walder Claire , Vane John R. 
Published: July 2012

The effects of sodium nitroprusside, acetylcholine and bradykinin on cardiac output and its distribution were studied in the anaesthetized, vagotomised rat preparation by use of 113Sn‐labelled microspheres.
All three vasodilators lowered peripheral arterial blood pressure, but only bradykinin significantly reduced total peripheral resistance without reducing cardiac output. Bradykinin caused tachycardia, but this was offset by a reduction in stroke volume. These effects of bradykinin were not altered by indomethacin (4 mg kg−1). Acetylcholine and sodium nitroprusside both caused significant (P > 0.05) reductions in stroke volume and cardiac output.
Bradykinin reduced vascular resistance in the liver, stomach, small intestine, large intestine, pancreas/mesentery, epididimides, skeletal muscle and fat. These responses were not affected by indomethacin, whereas, the reduction in vascular resistance in the brain induced by bradykinin was abolished by indomethacin.
Acetylcholine caused a reduction in renal vascular resistance, where bradykinin had no effect. However, acetylcholine did not cause any haemodynamic changes in the bradykinin‐sensitive intestinal vasculature.
Acetylcholine caused vasoconstriction in the coronary and epididymal vasculature. Bradykinin in the presence of indomethacin induced vasoconstriction in the skin.
In conclusion, the data show that, with the possible exception of the brain and the skin, the vasodilator actions of bradykinin can adequately be transduced (presumably by endothelium‐derived relaxing factor, EDRF) in the absence of prostacyclin synthesis. Additionally, these results indicate that the vasculature of the stomach, pancreas/mesentery, epididimides and skeletal muscle are equally sensitive to both acetylcholine and bradykinin, whereas the kidneys showed selectivity towards acetylcholine and the intestines towards bradykinin. These results may indicate differential receptor populations.