Substance P enteric neurons mediate non-cholinergic transmission to the circular muscle of the guinea-pig intestine

Abstract

The sites of action and possible roles of substance P in contracting the circular muscle of the guinea-pig ileum were studied using two analogues of substance P that act as antagonists of some of its actions. These are D-Arg1, D-Pro2, D-Trp7,9, Leu11-substance P and D-Pro2, D-Trp7,9-substance P, referred to by the single letter amino acid codes for the substituting amino acids as (RPWWL)-SP and (PWW)-SP, respectively. Records of circular muscle activity were taken from strips of intestine free of mucosa and submucosa and from rings with all layers of intestine intact. Substance P was equally effective in contracting the circular muscle strips as it was in contracting the longitudinal muscle. The contractions of strips were not blocked by hyoscine (2 X 10(-6) M) or tetrodotoxin (6 X 10(-7) M), but were substantially reduced by (RPWWL)-SP (6.7 X 10(-6) M) or (PWW)-SP (2 X 10(-5) M). In contrast, contractions of the circular muscle of whole rings of intestine elicited by low concentrations of substance P (4 X 10(-7) M) were blocked by hyoscine or tetrodotoxin but not reduced by the substance P antagonists in the concentrations referred to above. These observations indicate that the antagonists are effective at receptors for substance P on the muscle, but not at substance P receptors on enteric cholinergic nerves. Transmural stimulation of strips of circular muscle or of intestinal rings in the presence of hyoscine evoked contractions that were blocked by tetrodotoxin. These hyoscine-resistant, nerve-mediated contractions could be elicited by single pulses in the strips.(ABSTRACT TRUNCATED AT 250 WORDS)