The mechanism of action of dopamine to inhibit field stimulation-induced contractions of guinea pig stomach strips.

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 alpha 2-agonist guanfacine and partially antagonised by the alpha 2-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 alpha 2-adrenoceptor mechanisms. A failure of phenylephrine to mimic, or prazosin to attenuate the agonist inhibitory responses would not indicate an additional alpha 1-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 alpha 1-adrenoceptor stimulation but may involve an action on alpha 2-adrenoceptors.