The β‐adrenoceptors mediating relaxation of rat oesophageal muscularis mucosae are predominantly of the β3‐, but also of the β2‐subtype

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Abstract
β‐Adrenoceptor‐mediated relaxation of rat oesophageal smooth muscle was investigated by studying the effects of β1‐ and β2‐selective antagonists on the relaxation induced by (−)‐isoprenaline, the β2‐selective agonists fenoterol and clenbuterol and the β3‐agonist, BRL 37344. The highly β1‐selective antagonist CGP 20712A did not antagonize (−)‐isoprenaline‐ or BRL 37344‐induced relaxations in concentrations up to 10 μm. Only at 100 μm of CGP 20712A were clear rightward shifts of the agonist concentration‐response curves (CRCs) observed, with pA2 values of 4.70 and 4.97 against (−)‐isoprenaline and BRL 37344, respectively. ICI 118,551, a potent and selective β2‐antagonist, at 100 nm 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 μm 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 μm ICI 118,551, yielding a pA2 value of 5.48. These results clearly demonstrate that the BRL 37344‐induced relaxation of rat oesophageal muscularis mucosae is mediated solely through β3‐adrenoceptors, whereas (−)‐isoprenaline‐, fenoterol‐ and clenbuterol‐induced relaxations were shown to involve both β2‐ and, predominantly, β3‐adrenoceptors.