Postsynaptic enhancement by motilin of muscarinic receptor cation currents in duodenal smooth muscle

We have investigated a potential role of motilin in amplifying the postsynaptic muscarinic responses in the rabbit duodenal smooth muscle cells, using the whole cell variant of patch-clamp technique. Stimulation of motilin receptors by exogenously applied motilin (1 nM) resulted in a large increase in carbachol (CCh)-induced atropine-sensitive cation current (I-CCh) at threshold concentrations of CCh (0.3-1 mu M) at 30 degrees C. This potentiation was abolished in the presence of a specific blocker of motilin receptor (GM109) and was attenuated with increased concentrations of either motilin or CCh, being virtually absent with maximally effective concentrations of these agonists. Motilin failed to potentiate I-CCh when the ambient temperature was reduced to 20 degrees C or if the cation current had been directly activated by internal perfusion with guanosine 5'-O-(3-thiotriphosphate) (50 mu M) bypassing the muscarinic receptor. These results suggest that some biochemical processes, such as enzymatic reactions, might be involved in the motilin-induced potentiation and that its site of action might be the muscarinic receptor and/or associated G proteins.