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The β‐adrenoceptors mediating relaxation of rat oesophageal muscularis mucosae are predominantly of the β3‐, but also of the β 2 ‐subtype
Author(s) -
Boer Robert E.P.,
Brouwer Frans,
Zaagsma Johan
Publication year - 1993
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.1476-5381.1993.tb13830.x
Subject(s) - fenoterol , isoprenaline , clenbuterol , endocrinology , agonist , medicine , antagonist , schild regression , chemistry , receptor , stimulation , asthma
1 β‐Adrenoceptor‐mediated relaxation of rat oesophageal smooth muscle was investigated by studying the effects of β 1 ‐ and β 2 ‐selective antagonists on the relaxation induced by (−)‐isoprenaline, the β 2 ‐selective agonists fenoterol and clenbuterol and the β 3 ‐agonist, BRL 37344. 2 The highly β 1 ‐selective antagonist CGP 20712A did not antagonize (−)‐isoprenaline‐ or BRL 37344‐induced relaxations in concentrations up to 10 μ m . Only at 100 μ m of CGP 20712A were clear rightward shifts of the agonist concentration‐response curves (CRCs) observed, with pA 2 values of 4.70 and 4.97 against (−)‐isoprenaline and BRL 37344, respectively. 3 ICI 118,551, a potent and selective β 2 ‐antagonist, at 100 n m caused moderate rightward shifts of the CRCs of (−)‐isoprenaline, fenoterol and clenbuterol; with fenoterol and clenbuterol, this was accompanied by a clear steepening of the curve. Only at the highest concentration (100 μ m ICI 118,551) did the shifts to the right further increase substantially. Resulting Schild‐plots were clearly biphasic. BRL 37344‐induced relaxations were only antagonized at 100 μ m ICI 118,551, yielding a pA 2 value of 5.48. 4 These results clearly demonstrate that the BRL 37344‐induced relaxation of rat oesophageal muscularis mucosae is mediated solely through β 3 ‐adrenoceptors, whereas (−)‐isoprenaline‐, fenoterol‐ and clenbuterol‐induced relaxations were shown to involve both β 2 ‐ and, predominantly, β 3 ‐adrenoceptors.