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β 2 ‐Adrenoceptors mediate inhibition of carbachol‐induced contraction and cAMP generation in isolated smooth muscle cells from rabbit gastric antrum
Author(s) -
Moummi Chafiq,
Magous Richard,
Bali JeanPierre
Publication year - 1992
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.430270206
Subject(s) - carbachol , endocrinology , medicine , contraction (grammar) , agonist , chemistry , adrenergic , receptor , biology , stimulation
The regulation of inhibition of carbachol‐induced contraction by β‐adrenoceptors of rabbit gastric antrum has been investigated. A functional assay using isolated smooth muscle cells (ISMC) was used to study the effect of β‐adrenergic agonists and antagonists on carbacholcontracted ISMC and cAMP generation. The nonselective β‐adrenergic agonist isoproterenol caused concentration‐related inhibition of carbachol‐induced contraction associated with a significant increase in cellular cAMP. The EC 50 for the effect of isoproterenol on cell inhibition of carbachol‐induced contraction was closely related to the EC 50 for cAMP formation; the two curves were superimposable, indicating a positive correlation between the biological activity (inhibition of carbachol‐induced contraction) and the intracellular event (cAMP formation) caused by the activation of β‐adrenoceptors. The Kinetic studies demonstrate that maximum inhibition of carbachol‐induced contraction and a parallel elevation of intracellular cAMP content were reached at 30 sec of incubation with isoproterenol. The β 2 ‐selective receptor agonist terbutaline induced inhibition of carbachol‐induced contraction of carbachol‐contracted ISMC and cAMP generation. However, the relatively β 1 ‐selective receptor agonist norepinephrine had no significant effect. Propranolol, a nonselective β‐ adrenoceptor antagonist (β 1 and β 2 ) caused a significant inhibition of the carbacholβ 2 induced contraction and rise in cAMP induced by isoproterenol and terbutaline, while the β 1 ‐selective adrenergic receptorantagonist metoprolol, even at higher concentration, was inactive. These data demonstrate that there is a correlation between inhibition of carbachol‐induced contraction and cAMP generation upon activation of the β 2 ‐adrenoreceptors in the ISMC of rabbit gastric antrum. © 1992 Wiley‐Liss, Inc.