Circular Muscle Of Guinea-pig Stomach Research Articles

Mechanism of acetylcholine-induced depolarization in the antral circular muscle of guinea-pig stomach

Mechanism of acetylcholine-induced depolarization in the antral circular muscle of guinea-pig stomach

The M3 muscarinic receptor links to three different transduction mechanisms with different efficacies in circular muscle of guinea-pig stomach.

1. In a previous publication, we showed that 10 microM carbachol induced contraction by activating three independent transduction mechanisms in circular smooth muscle of guinea-pig gastric fundus (Parekh & Brading, 1991). These were: inositol trisphosphate-mediated intracellular Ca2+ release, Ca2+ influx through a nifedipine-sensitive route and Ca2+ influx through a receptor operated nifedipine-insensitive pathway. The former two processes contribute to the phasic contraction and the latter two to the tonic contraction. In this paper, we have studied the effects of muscarinic receptor antagonists with known selectivity for different muscarinic receptor subtypes, on the contraction evoked by 10 microM carbachol. 2. Low concentrations of pirenzepine (M1 selective) had little effect on the contraction initiated by carbachol. Higher concentrations (greater than 1 microM) reduced only the phasic component. This concentration of pirenzepine greatly reduced the contraction evoked by 10 microM carbachol in Ca(2+)-free solution, indicating inhibition of intracellular Ca2+ release. 3. In the presence of 10 microM nifedipine, the tonic contraction evoked by 10 microM carbachol (reflecting the receptor-operated nifedipine-insensitive route) was abolished by 10 microM pirenzepine. In the absence of nifedipine pretreatment, however, 10 microM pirenzepine did not abolish the contraction to 10 microM carbachol. This contraction was subsequently abolished by nifedipine. 4. Only high concentrations (greater than 10 microM) of the M2-selective antagonist, gallamine, inhibited the contraction to 10 microM carbachol. Like pirenzepine, gallamine preferentially inhibited the phasic component of the contraction, indicating an effect on intracellular Ca2+ release. 5. The non-selective muscarinic receptor antagonist, atropine, abolished all components of the contraction. At low concentrations, atropine also reduced the phasic component without affecting the tonic one, indicating preferential inhibition of intracellular Ca2+ release.6. It is concluded that (i) the different transduction mechanisms have different sensitivities to the antagonists used and (ii) an M3 receptor activates the three transduction mechanisms with different efficacies.

Mechanical and electrical responses to alpha-adrenoceptor activation in the circular muscle of guinea-pig stomach.

1 In the circular muscle of the corpus region of the guinea-pig stomach, the effects of catecholamines on mechanical activity were studied with simultaneous recording of membrane potential by use of intracellular microelectrodes. In order to investigate responses mediated through alpha-adrenoceptors, the beta-adrenoceptors were blocked by propranolol (10(-6) M) in most experiments. 2 Adrenaline (less than 10(-6) M) produced a monophasic contraction with little change in membrane potential. At higher concentrations (greater than 10(-5) M), adrenaline usually produced an early transient contraction followed by a slow tonic contraction. During the early phase, the membrane was hyperpolarized and slow waves were reduced in amplitude. 3 The phasic contractions superimposed on the late slow phase of the contractile response were higher in frequency and larger in amplitude than in controls before adrenaline application. These changes were associated with an increase in the amplitude and frequency of slow waves, and with a spike-like component appearing on the top of each slow wave. 4 Adrenaline-induced changes in mechanical and electrical activity were inhibited by prazosin, but largely unaffected by yohimbine. In some preparations, there was a transient weak inhibition of phasic contraction before muscle tone was increased by adrenaline, and this became more pronounced in the presence of yohimbine. 5 Phenylephrine, selective for alpha 1-receptors, produced responses very similar to those of adrenaline, whereas agonists selective for alpha 2-receptors, clonidine and B-HT 920, produced only a small slow contraction without any clear change in membrane potential. 6 It is concluded that in the circular muscle of guinea-pig stomach, the contractile response and changes in the electrical slow wave activity produced by adrenaline are both mediated mainly through the activation of alpha-receptors.

P-122 - AlPha-adrenergic responses in circular muscle of guinea-pig stomach

P-122 - AlPha-adrenergic responses in circular muscle of guinea-pig stomach

Neuronally mediated contraction responses of guinea-pig stomach smooth muscle preparations: Modification by benzamide derivatives does not reflect a dopamine antagonist action

The actions of the substituted benzamide derivatives metoclopramide, clebopride, YM-09151-2, tiapride, (+)- and (−)-sulpiride and (+)- and (−)-sultopride, and the dopamine antagonists haloperidol and domperidone, were studied on the responses to field stimulation (0.125–10 Hz) of smooth muscle strips taken from cardia, fundus, body and antral regions of the longitudinal and circular muscle of guinea-pig stomach. Field stimulation of the longitudinal strips caused contraction responses which were antagonised by atropine (but not by prazosin, yohimbine, propranolol or methysergide) to indicate a muscarinic cholinergic involvement. Antagonism of the contractions revealed or enhanced relaxation responses mediated via unidentified mechanisms (resistant to cholinergic and adrenergic antagonists). Metoclopramide enhanced the field stimulation-induced contractions of the stomach smooth muscle preparations via atropine sensitive mechanisms but failed to attenuate the field stimulation-induced relaxation responses. Clebopride's action closely followed that of metoclopramide but YM-09151-2 only enhanced the contraction responses of the longitudinal muscle preparations. Other dopamine antagonists, (+)- and (−)-sulpiride, (+)- and (−)-sultopride, tiapride, haloperidol and domperidone failed to facilitate contraction to field stimulation of any stomach tissue. Thus, the actions of metoclopramide, clebopride and YM-09151-2 to facilitate contraction to field stimulation of stomach smooth muscle are mediated via muscarinic cholinergic mechanism and are not the consequence of an antagonism at any recognisable dopamine receptor.

The slow wave in the circular muscle of the guinea-pig stomach.

The slow wave in the circular muscle of guinea-pig stomach was investigated with the double sucrose-gap method. 2. The amplitude of the slow wave was reduced by depolarization, and it was increased by a small hyperpolarization (5-10 mV). With hyperpolarization greater than 15 mV the amplitude decreased, and the slow wave became reduced, and less dependent on polarization. This residual was not abolished by strong hyperpolarizing current pulses. 3. The frequency of the slow waves was not much affected by membrane polarization. The change was only 15-20% by depolarization or hyperpolarization of 12mV. 4. Rythmic inward currents could be recorded under voltage-clamp conditions. The frequency of the inward currents was the same as that of the slow wave. The intensity of inward current was little affected by membrane polarization. 5. Lowering the temperature reduced the frequency of the slow wave. The rates of rise and fall of the component which remained during strong hyperpolarization were similarly decreased by lowering the temperature. The Q10 of the frequency was about 2-7. 6. It is suggested that the slow wave consists of two different components. One is generated by a potential independent process, and triggers the second component which is potential dependent. The first component may be controlled by some metabolic process.