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Field stimulation (0.125-10 Hz) of longitudinal smooth muscle strips taken from the fundus of guinea pig stomach caused frequency related contraction responses (atropine-sensitive) associated with relaxation at the higher frequencies (both responses tetrodotoxin-sensitive). Dopamine, noradrenaline, adrenaline and apomorphine antagonised the contraction responses at all frequencies; the concentration-response curves were steep and the use of higher concentrations was precluded by changes in base line tension per se. That noradrenaline was approximately 10 fold more potent than dopamine, that the dopamine response was not antagonised by the dopamine antagonists haloperidol, domperidone or (-)sulpiride, but was mimicked by the α-agonist guanfacine and partially antagonised by the α-adrenoceptor antagonist yohimbine (which could also antagonise the inhibitory actions of guanfacine) would indicate that a component of dopamine's action to reduce cholinergic activity is effected via α-adrenoceptor mechanisms. A failure of phenylephrine to mimic, or prazosin to attenuate the agonist inhibitory responses would not indicate an additional α-adrenoceptor involvement. The persistence of the dopamine response following disruption of noradrenergic function by reserpine or inhibition of catecholamine reuptake processes (desmethylimipramine plus corticosterone, GBR 13098) would indicate a direct action of dopamine. It is concluded that the ability of dopamine to reduce cholinergic induced contractions in longitudinal smooth muscle of the stomach does not reflect a dopamine receptor or α-adrenoceptor stimulation but may involve an action on α-adrenoceptors. [ABSTRACT FROM AUTHOR]

Field stimulation of circular smooth muscle of guinea-pig stomach from the regions of the cardia and fundus caused contraction responses at low stimulation frequencies (0.25-1 Hz) with relaxation at higher frequencies (1-10 Hz), whilst tissues of the body and antrum responded with contraction throughout the frequency range. Atropine (10-10 M) antagonised the contraction responses of all tissues, with relaxation developing at higher concentrations (except for antral tissue). In contrast, metoclopramide (10-10 M) caused modest (cardia, fundus) or marked (body, antrum) enhancement of contractions to field stimulation, whilst domperidone (10-10 M), haloperidol (10-10 M), prazosin, propranolol and methysergide (10-10 M) failed to modify the contraction responses. However, whilst yohimbine and guanethidine failed to modify the contractions of the cardia, fundus and body tissues, those of the antral preparations were antagonised by nanomolar concentrations of yohimbine and by guanethidine (10-5×10 M). To optimise the relaxation responses for study, atropine was included in the physiological solution. Relaxation to field stimulation of preparations from the body and cardia, but not the fundus, was antagonised by reserpine pretreatment (5 mg/kg i.p., 24h), addition of guanethidine (10-10 M), phentolamine, prazosin or propranolol (10-10 M) (the effects of prazosin and propranolol being additive). Higher concentrations of haloperidol and domperidone antagonised the relaxation responses of the body preparations only. Metoclopramide, yohimbine and methysergide (10-10 M) were ineffective. Thus, it is concluded that the contractile effects of the 4 stomach areas to field stimulation reflects a major cholinergic involvement, with an additional α-adrenoceptor contractile component in antral tissue. Relaxation responses of cardia and body tissue involve α- and β-adrenoceptors plus a further, unidentified, non-adrenergic component; the latter represents the total relaxation response of the fundic preparation. [ABSTRACT FROM AUTHOR]