AJP - Gastrointestinal and Liver Physiology, Vol 262, Issue 3 461-G469, Copyright © 1992 by American Physiological Society
Characterization of opioid receptors on smooth muscle cells from guinea pig stomach
L. Zhang, Z. F. Gu, T. Pradhan, R. T. Jensen and P. N. Maton
Digestive Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892.
On the basis of opioid-stimulated contraction of dispersed gastric smooth
muscle cells it has been suggested that these cells possess opioid
receptors of three subtypes: kappa (kappa), mu (mu), and delta (delta). We
have used selective peptidase-resistant radioligands, agonists and
antagonists, to examine receptor subtypes on dispersed gastric smooth
muscle cells from guinea pigs prepared by collagenase digestion. The
kappa-agonist U-50488H, the mu-agonist [D-Ala2,N-Me-Phe4,Gly5-ol]enkephalin
(DAGO), and the delta-agonist [D-Pen2,Pen5]enkephalin (DPDPE) each caused
muscle contraction. The concentrations required to caused half-maximal
contraction were U50488H (6 pM) greater than DAGO (13 pM) greater than
DPDPE (6 nM). The abilities of these agonists to inhibit binding of
[3H]U-69593 (kappa-preferring) by 50% were U50488H (43 nM) greater than
DAGO (43 microM) greater than DPDPE (200 microM). Their abilities to
inhibit binding of [3H]naloxone (mu-preferring) by 50% were DAGO (0.2
microM) greater than U50488H (10 microM) greater than DPDPE (greater than
100 microM). No binding could be detected with the delta-selective ligand
[3H]DPDPE. The kappa-preferring antagonist Mr2266 (10 nM) preferentially
inhibited contraction stimulated by the kappa-agonist U50488H, and
naltrexone (10 nM) (mu-selective antagonist) preferentially inhibited
contraction stimulated by the mu-agonist DAGO. ICI 174864 (200 microM;
delta-selective antagonist) had no effect on contraction stimulated by mu-,
kappa-, or delta-agonists. Contraction stimulated by the delta-agonist
DPDPE was inhibited by both kappa- and mu-receptor antagonists. Studies on
the effect of the antagonists on binding of [3H]naloxone and [3H]U69593
also provided evidence for kappa- and mu-sites but nor for
delta-sites.(ABSTRACT TRUNCATED AT 250 WORDS)
