Calcium-dependent presynaptic action of substance P at the frog neuromuscular junction

Abstract

SUBSTANCE P, an 11 amino acid peptide found in many areas of the nervous system¹, has been proposed to be the excitatory transmitter between primary afferents and motoneurons². A depolarising action of substance P on spinal motoneurons and primary afferents has been demonstrated^3–6. But, an initial reduction of response preceding an increased spinal reflex discharge and a reduction of the motoneurone excitatory postsynaptic potential has also been seen in response to substance P (refs 4, 5). In addition, both excitatory and inhibitory effects of substance P on firing of cuneate and cortical Betz cells have been reported^7,8. In the hatchetfish Mauthner fibre–giant fibre synapse, substance P has a pronounced presynaptic effect⁹. We have further investigated the effects of substance P at a synapse in which the electrophysiological characteristics and transmitter are known, the ionic constituents of the Ringer can be manipulated and quantal analysis is possible—the neuromuscular junction of the frog. We report here that substance P has a potent presynaptic effect on transmission at this synapse which is composed of an initial phase in which transmission is depressed, followed by a prolonged period in which excitability and quantal release are increased.