AJP - Gastrointestinal and Liver Physiology, Vol 261, Issue 3 464-G469, Copyright © 1991 by American Physiological Society
Functional subtyping of muscarinic receptors on canine esophageal mucosa
R. Lad, B. Donoff and P. K. Rangachari
Intestinal Disease Research Unit, McMaster University, Hamilton, Ontario, Canada.
Serosal addition of muscarinic agonists elicited rapid changes in
electrical parameters across the isolated canine esophageal epithelium set
up in vitro. Both carbachol and the M1-selective agonist, McNeil A343
(McN), increased transmucosal potential differences (PDs), decreased
transmucosal resistances (R), and increased short-circuit currents (Isc).
Carbachol was more potent and more effective than McN. Muscarinic
antagonists were used to define the muscarinic receptor involved. The pA2
values obtained with Schild plots were as follows: atropine 9.14, 4-DAMP
8.98, AFDX-116 6.71, and pirenzepine 7.12. Low concentrations of
pirenzepine (10(-8) M), produced a rightward shift in the dose-response
curve to McN, without inhibiting responses to carbachol. Thus the receptor
subtype is clearly not an M2. As in other glandular systems, M3 receptors
are present. Whether M1 receptors also exist requires better definition of
receptor densities-reserves in this tissue. Carbachol induced net secretion
of Na and Cl and converted a predominantly absorptive tissue to a secretory
one.
