Comparison of human and porcine gastric clasp and sling fiber contraction by M2and M3muscarinic receptors

Author:

Vegesna Anil K.1,Braverman Alan S.2,Miller Larry S.1,Tallarida Ronald J.34,Tiwana Mansoor I.1,Khayyam Umar1,Ruggieri Michael R.23

Affiliation:

1. Departments of 1Medicine,

2. Urology, and

3. Pharmacology and

4. Center for Substance Abuse, Temple University School of Medicine, Philadelphia, Pennsylvania

Abstract

To compare the gastroesophageal junction of the human with the pig, M2and M3receptor densities and the potencies of M2and M3muscarinic receptor subtype selective antagonists were determined in gastric clasp and sling smooth muscle fibers. Total muscarinic and M2receptors are higher in pig than human clasp and sling fibers. M3receptors are higher in human compared with pig sling fibers but lower in human compared with pig clasp fibers. Clasp fibers have fewer M3receptors than sling fibers in both humans and pigs. Similar to human clasp fibers, pig clasp fibers contract significantly less than pig sling fibers. Analysis of the methoctramine Schild plot suggests that M2receptors are involved in mediating contraction in pig clasp and sling fibers. Darifenacin potency suggests that M3receptors mediate contraction in pig sling fibers and that M2and M3receptors mediate contraction in pig clasp fibers. Taken together, the data suggest that both M2and M3muscarinic receptors mediate the contraction in both pig clasp and sling fibers similar to human clasp and sling fibers.

Publisher

American Physiological Society

Subject

Physiology (medical),Gastroenterology,Hepatology,Physiology

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