Am J Physiol. 1989 Sep;257(3):G447-53. doi: 10.1152/ajpgi.1989.257.3.G447.

Substance P: mechanism of action and receptor distribution at the feline ileocecal sphincter region.

The American journal of physiology

R D Rothstein, E Johnson, A Ouyang

PMID: 2476938 DOI: 10.1152/ajpgi.1989.257.3.G447

Abstract

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.

Substances

• Receptors, Neurokinin-1
• Receptors, Neurotransmitter
• Substance P

MeSH terms

• Animals
• Autoradiography
• Cats
• Colon / drug effects
• Colon / ultrastructure
• Ileocecal Valve / analysis
• Ileocecal Valve / drug effects
• Ileocecal Valve / ultrastructure
• Ileum / drug effects
• Ileum / ultrastructure
• Male
• Receptors, Neurokinin-1
• Receptors, Neurotransmitter / analysis
• Substance P / pharmacology

Publication Types

• Journal Article
• Research Support, U.S. Gov't, P.H.S.

Grant support

• 5KD4-DK-01616/DK/NIDDK NIH HHS/United States
• DK-07066-13/DK/NIDDK NIH HHS/United States

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