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Characterization of catecholamine‐mediated relaxations in rat isolated gastric fundus: evidence for an atypical β‐adrenoceptor
Author(s) -
McLaughlin Daniel P.,
MacDonald Allan
Publication year - 1991
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1991.tb09792.x
Subject(s) - prazosin , isoprenaline , propranolol , endocrinology , agonist , medicine , chemistry , yohimbine , schild regression , pharmacology , receptor , biology , antagonist , stimulation
1 Experiments were carried out in order to characterize the receptors mediating relaxant responses to catecholamines in the rat gastric fundus. The effects of noradrenaline, isoprenaline and the ‘atypical’ or β 3 ‐adrenoceptor agonist, BRL 37344, on methacholine‐induced tone were measured. Prazosin, propranolol and cyanopindolol were used as antagonists. 2 Relaxant responses to noradrenaline, in the presence of propranolol (1 μ m ) were antagonized in a concentration‐dependent manner by prazosin (0.01 to 1 μ m ), although this antagonism was weak and non‐competitive in nature. Relaxant responses to isoprenaline, in the presence of prazosin (0.1 μ m ), were antagonized only by the highest concentration of propranolol (1 μ m ) giving a pK B of 6.3. BRL 37344 also relaxed the rat gastric fundus in the presence of prazosin (0.1 μ m ), and the responses to BRL 37344 were unaffected by propranolol (1 μ m ). 3 Tachyphylaxis to BRL 37344 was observed, a second concentration‐response curve being significantly shifted to the right. Exposure of tissues to BRL 37344 (1 μ m ) between concentration‐response curves also caused an 11 fold rightward shift in the response to isoprenaline. 4 In the presence of prazosin (0.1 μ m ) and propranolol (1 μ m ), the rank order of potency of the agonists was: (–)‐isoprenaline (1.0) > (–)‐noradrenaline (0.39) > BRL 37344 (0.10). 5 Responses to BRL 37344 in the presence of prazosin (0.1 μ m ) and propranolol (1 μ m ) were antagonized by (±)‐cyanopindolol (1 μ m ), with a pK B of 6.56. Responses to isoprenaline, under the same conditions, were antagonized in a competitive manner by (±)‐cyanopindolol (0.1–1 μ m ), with the slope of a Schild plot close to unity and a pA 2 value of 7.44. 6 The resistance to blockade by prazosin and propranolol and the antagonism by cyanopindolol of the responses mediated by isoprenaline and BRL 37344 suggest that atypical β‐adrenoceptors similar to ‘atypical’ β‐adrenoceptors in rat adipocytes and other tissues are present in the rat gastric fundus.