Haloperidol, chlorpromazine and lithium chloride antagonize the excitatory action of forskolin and of some gut peptides on guinea-pig myenteric neurones

Abstract

The effects of haloperidol, chlorpromazine and lithium chloride on electrical behaviour of AH/type 2 myenteric neurones from guinea-pig ileum as well as on the excitatory action of forskolin and of some gut peptides were studied. Haloperidol and chlorpromazine decreased the excitability of AH/type 2 myenteric neurones which was evidenced from the inhibition of spontaneous and electrically-evoked action potentials recorded intracellularly from neurones. Forskolin caused excitation in AH/type 2 neurones which mimicked the changes in neuronal behaviour that occur during the slow synaptic excitatory potentials (EPSP) in the same type of neurones: membrane depolarization, augmented excitability and increased input membrane resistance. Haloperidol, chlorpromazine and lithium chloride blocked the excitatory action of forskolin. Vasoactive intestinal polypeptide (VIP), cholecystokinin (CCK) and bombesin excited the AH/type 2 myenteric neurones in a manner similar to that of forskolin. Haloperidol and chlorpromazine antagonized the excitatory actions of VIP, CCK, and bombesin. The results indicated that the antipsychotic drugs tested decrease the excitability of the AH/type 2 myenteric neurones and this could partly account for their side effects observed in clinical practice. The present data provided supporting evidence for the role of cyclic adenosine-3', 5'-monophosphate (cyclic AMP) in the regulation of excitability of AH/type 2 myenteric neurones and for the function of cyclic AMP as a second messenger in the action of some gut peptides.