Modulation of cholinergic transmission by substance P.

Substance P administered iontophoretically to Renshaw cells in the cat had a dual effect, sometimes causing excitation and at other times inhibiting the excitatory effect of acetylcholine (ACh). The inhibitory effect was selective for the nicotinic receptors on Renshaw cells and the excitatory effect seemed to be due to the release of ACh from cholinergic terminals. It has not been possible to demonstrate a similar inhibitory effect on nicotinic receptors at the neuromuscular junction in frogs or in the chick, although a small agonist effect was occasionally observed. In the atropinized cat, intra-arterial injections of ACh to the superior cervical ganglion cause both a rise in blood pressure and contractions of the nictitating membrane which are abolished by hexamethonium. Intra-arterial injections of substance P partially blocked these nicotinic actions of ACh, but no excitatory effect of substance P was observed. These observations are discussed in relation to other studies and indicate that the polypeptide could function as an inhibitory or facilitatory regulator of cholinergically mediated responses at some but not all cholinergic synapses.