Evidence that substance P does not mediate slow synaptic excitation within the myenteric plexus

Abstract

ELECTRICAL stimulation of presynaptic fibres to the so-called AH¹ or type II² myenteric neurones in guinea pig small intestine evokes a slow excitatory postsynaptic potential (e.p.s.p.) characterised by long-lasting depolarisation associated with increased membrane resistance and augmented excitability³. Two substances have been implicated as possible neurotrans-mitters for the slow e.p.s.p. Katayama and North reported that application of substance P to myenteric neurones mimicked the slow e.p.s.p.⁴, and J.D.W. and C.J.M. presented several lines of evidence for serotonin as the transmitter substance^5,6. We now report that methysergide, a drug which abolishes both the slow e.p.s.p. and the action of exogenous serotonin^5,6, does not affect the action of substance P on guinea pig myenteric neurones. The results suggest that substance P is unlikely to be the neuro-transmitter which mediates the slow e.p.s.p.