Substance P: mechanism of action and receptor distribution at the feline ileocecal sphincter region.
The purpose of this study was to determine the mechanism of action of substance P at the distal ileum, ileocecal sphincter (ICS), and proximal colon in the cat and to determine the localization of substance P receptors at these sites by autoradiography. Intraluminal pressures and myoelectric activity were recorded at the feline distal ileum, ICS, and colon. Substance P caused a tonic and phasic spike-dependent contractile response at all three sites. The antagonists propranolol, phentolamine, and naloxone did not affect the contractile response to substance P at the ileum, ICS, or colon. The ganglionic blocker trimethaphan camsylate potentiated the response to substance P at all three sites, P less than 0.05. Both atropine and tetrodotoxin reduced the response of substance P at the ileal site. At the ICS, atropine or tetrodotoxin reduced, but did not obliterate, the effect of substance P. Neither atropine nor tetrodotoxin reduced substance P-induced colonic contractions. By use of autoradiography, specific binding for substance P was determined to be present at all three sites with the greatest concentration of substance P receptors in the circular muscle layer. In conclusion, these studies suggest multiple sites of action of substance P. At the ileum, substance P causes contraction via a cholinergic pathway. At the ICS, substance P has an excitatory action through a cholinergic pathway and also at smooth muscle receptors. In the proximal colon, the excitatory action of substance P is via smooth muscle receptors. An inhibitory ganglionic pathway also exists at all three sites. Substance P receptors exist predominantly in the circular muscle region of the ileum, ICS, and the proximal colon.
Rothstein
R D
RD
Department of Medicine, University of Pennsylvania, Hospital of University of Pennsylvania, Philadelphia 19104.
Johnson
E
E
Ouyang
A
A
D000818:Animals; D001345:Autoradiography; D002415:Cats; D003106:Colon / Q000187:drug effects / Q000648:ultrastructure; D007080:Ileocecal Valve / Q000032:analysis / Q000187:drug effects / Q000648:ultrastructure*; D007082:Ileum / Q000187:drug effects / Q000648:ultrastructure; D008297:Male; D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter / Q000032:analysis*; D013373:Substance P / Q000494:pharmacology*
D018040:Receptors, Neurokinin-1; D017981:Receptors, Neurotransmitter; D013373:Substance P