Roles of Substance P Receptors in Human Colon Circular Muscle: Alterations in Diverticular Disease

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.

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Distribution of vasoactive intestinal polypeptide and substance P receptors in human colon and small intestine

Digestive Diseases and Sciences ◽

10.1007/bf01536382 ◽

1989 ◽

Vol 34 (7) ◽

pp. 1100-1108 ◽

Cited By ~ 23

Author(s):

Louis Y. Korman ◽

Hassan Sayadi ◽

Barbara Bass ◽

Terry W. Moody ◽

John W. Harmon

Keyword(s):

Small Intestine ◽

Substance P ◽

Vasoactive Intestinal Polypeptide ◽

Human Colon ◽

Substance P Receptors ◽

Intestinal Polypeptide

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Morphology of the canine pyloric sphincter in relation to function

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y89-251 ◽

1989 ◽

Vol 67 (12) ◽

pp. 1560-1573 ◽

Cited By ~ 27

Author(s):

E. E. Daniel ◽

I. Berezin ◽

H. D. Allescher ◽

H. Manaka ◽

V. Posey-Daniel

Keyword(s):

Smooth Muscle ◽

Substance P ◽

Smooth Muscle Cells ◽

Gap Junctions ◽

Vasoactive Intestinal Polypeptide ◽

Interstitial Cells Of Cajal ◽

Circular Muscle ◽

Interstitial Cells ◽

Pyloric Sphincter ◽

Cells Of Cajal

The ultrastructure and immunocytochemistry of the canine distal pyloric muscle loop, the pyloric sphincter, were studied. Cells in this muscle were connected by gap junctions, fewer than in the antrum or corpus. The sphincter had a dense innervation and a sparse population of interstitial cells of Cajal. Most such cells were of the circular muscle type but a few were of the type in the myenteric plexus. Nerves were sometimes associated with interstitial cell profiles, but most nerves were neither close to nor associated with interstitial cells nor close to smooth muscle cells. Nerve profiles were characterized by an unusually high proportion of varicosities with a majority or a high proportion of large granular vesicles. Many of these were shown to contain material immunoreactive for vasoactive intestinal polypeptide (VIP) and some had substance P (SP) immunoreactive material. All were presumed to be peptidergic. VIP was present in a higher concentration in this muscle than in adjacent antral or duodenal circular muscle. Interstitial cells of Cajal made gap junctions to smooth muscle and to one another and might provide myogenic pacemaking activity for this muscle, but there was no evidence of a close or special relationship between nerves with VIP or SP and these cells. The absence of close relationships between nerves and either interstitial cells or smooth muscle cells leaves unanswered questions about the structural basis for previous observations of discrete excitatory responses or pyloric sphincter to single stimuli or nerves up to one per second. In conclusion, the structural observations suggest that this muscle has special neural and myogenic control systems and that interstitial cells may function to control myogenic activity of this muscle but not to mediate neural signals.Key words: vasoactive intestinal polypeptide, interstitial cells of Cajal, neuropeptides, gap junctions, substance P.

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Substance P receptors: Localization by light microscopic autoradiography in rat brain using [3H]SP as the radioligand

Brain Research ◽

10.1016/0006-8993(84)90470-0 ◽

1984 ◽

Vol 307 (1-2) ◽

pp. 147-165 ◽

Cited By ~ 183

Author(s):

Patrick W. Mantyh ◽

Stephen P. Hunt ◽

John E. Maggio

Keyword(s):

Substance P ◽

Rat Brain ◽

Substance P Receptors

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Structure, expression and second messenger mediated regulation of rat and human substance P receptors and their genes

Regulatory Peptides ◽

10.1016/0167-0115(92)90872-r ◽

1992 ◽

Vol 37 ◽

pp. S16

Author(s):

J.E. Krause ◽

Y. Takeda ◽

P. Blount ◽

B.S. Sachais ◽

R. Raddatz ◽

...

Keyword(s):

Substance P ◽

Second Messenger ◽

Substance P Receptors

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Exogenous glucagon-like peptide 1 reduces contractions in human colon circular muscle

Journal of Endocrinology ◽

10.1530/joe-13-0525 ◽

2014 ◽

Vol 221 (1) ◽

pp. 29-37 ◽

Cited By ~ 24

Author(s):

Antonella Amato ◽

Sara Baldassano ◽

Rosa Liotta ◽

Rosa Serio ◽

Flavia Mulè

Keyword(s):

Colonic Motility ◽

Circular Muscle ◽

Human Colon ◽

Inhibitory Effect ◽

Mechanical Activity ◽

Organ Bath ◽

Dependent Manner ◽

Double Labeling ◽

Glucagon Like Peptide ◽

Glucagon Like Peptide 1

Glucagon-like peptide 1 (GLP1) is a naturally occurring peptide secreted by intestinal L-cells. Though its primary function is to serve as an incretin, GLP1 reduces gastrointestinal motility. However, only a handful of animal studies have specifically evaluated the influence of GLP1 on colonic motility. Consequently, the aims of this study were to investigate the effects induced by exogenous GLP1, to analyze the mechanism of action, and to verify the presence of GLP1 receptors (GLP1Rs) in human colon circular muscular strips. Organ bath technique, RT-PCR, western blotting, and immunofluorescence were used. In human colon, exogenous GLP1 reduced, in a concentration-dependent manner, the amplitude of the spontaneous contractions without affecting the frequency and the resting basal tone. This inhibitory effect was significantly reduced by exendin (9–39), a GLP1R antagonist, which per se significantly increased the spontaneous mechanical activity. Moreover, it was abolished by tetrodotoxin, a neural blocker, or Nω-nitro-l-arginine – a blocker of neuronal nitric oxide synthase (nNOS). The biomolecular analysis revealed a genic and protein expression of the GLP1R in the human colon. The double-labeling experiments with anti-neurofilament or anti-nNOS showed, for the first time, that immunoreactivity for the GLP1R was expressed in nitrergic neurons of the myenteric plexus. In conclusion, the results of this study suggest that GLP1R is expressed in the human colon and, once activated by exogenous GLP1, mediates an inhibitory effect on large intestine motility through NO neural release.

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