Atypical beta-adrenoceptor- (beta 3-adrenoceptor) mediated relaxation of canine isolated bronchial smooth muscle

Abstract

To determine whether atypical beta-adrenoceptors (beta 3-adrenoceptors) exist in the airway smooth muscle, we studied isolated bronchial segments from dogs under isometric conditions in vitro. Addition of beta-adrenoceptor agonists produced a concentration-dependent relaxation of tissues precontracted with 10(-5) M acetylcholine, rank-order potency being isoproterenol (1) > or = salbutamol (0.95) > or = BRL 37344, a beta 3-selective adrenoceptor agonist (0.83) > norepinephrine (0.10). Under the condition that alpha- and beta 1-adrenoceptors had been blocked, the relaxant response to salbutamol was competitively antagonized by the beta 2-adrenoceptor antagonist ICI 118551 and the pA2 was 7.01 +/- 0.25 (SE), whereas the response to BRL 37344 was resistant, with an apparent pA2 of 5.66. However, cyanopindolol, an antagonist for atypical beta-adrenoceptors, antagonized the BRL-induced relaxation in a competitive manner, with a pA2 of 6.74 +/- 0.11. This pA2 was lower than that when salbutamol was used as an agonist (P < 0.05). Intracellular adenosine 3',5'-cyclic monophosphate (cAMP) levels were increased by BRL 37344 in a concentration-dependent fashion. These results suggest that beta 3-adrenoceptors may exist in canine bronchial smooth muscle and that the stimulation of this type of receptor causes a bronchodilation through a cAMP-dependent pathway.

Beta 3-adrenoceptor agonists, BRL 37344 and SR 58611A, do not induce relaxation of human, sheep and guinea-pig airway smooth muscle in vitro

“…Our results have clearly shown that in the three species studied, and under the experimental conditions selected, an intense relaxation of the bronchial smooth muscle can be obtained with salbutamol and isoprenaline, and that this effect is principally β 2 -adrenergic, since the relaxations induced by these substances are abolished by ICI 118,551 10 -6 M, a concentration at which this substance can be considered a specific antagonist of β 2 -adrenoceptors [10]. However, we observed that on sheep bronchi salbutamol has a partial agonistic effect that is weaker than in human and guinea pig bronchi, as testified by a lower Emax.…”

“…A recent paper by TAMAOKI et al [10] reported that β 3 -adrenoceptor stimulation mediated relaxation of isolated canine bronchial smooth muscle. The aim of the present study was to extend this observation to other species.…”

“…These receptors have been shown to be abundant in adipose tissue and in a number of gastrointestinal smooth muscle preparations, for example guinea-pig ileum [2], rat proximal colon [3,4], rat distal colon [5], rat jejunum [6] and rat gastric fundus [7]. They have also been identified in rat skeletal muscle [8], ferret tracheal epithelium [9], and canine airways [10].Furthermore, stimulation of β 3 -adrenoceptors has been shown to induce relaxation of the rat oesophageal muscularis mucosae [11], lipolysis in omental and subcutaneous human fat cells [12], and inotropic effects in human [13] and canine heart [14].In the lung, β 3 -adrenoceptor stimulation increases epithelial fluid movements in ferret trachea [9], and reduces the release of the tachykinins, substance P or neurokinin A, from C-fibre endings of the isolated guinea-pig main bronchus [15,16].A recent paper by TAMAOKI et al [10] reported that β 3 -adrenoceptor stimulation mediated relaxation of isolated canine bronchial smooth muscle. The aim of the present study was to extend this observation to other species.…”

“…These receptors have been shown to be abundant in adipose tissue and in a number of gastrointestinal smooth muscle preparations, for example guinea-pig ileum [2], rat proximal colon [3,4], rat distal colon [5], rat jejunum [6] and rat gastric fundus [7]. They have also been identified in rat skeletal muscle [8], ferret tracheal epithelium [9], and canine airways [10].…”

Clinical pharmacology of β3‐adrenoceptors

“…It has also been shown in dose in Finnish subjects showed that the mutation frequency was similar in non-diabetic subjects (12%) and subjects response studies with BRL 37344 in canine bronchial smooth muscle that b 3 -AR mediate bronchorelaxant with NIDDM (11%), although the mean age for onset of diabetes was lower in those with the mutation [ 42]. effects [30 ], whilst other data have suggested a role of b 3 -AR in mediation of prejunction inhibition of nonIn the non-diabetic subjects, those with the mutation exhibited a greater degree of obesity and impaired adrenergic non-cholinergic contraction in guinea-pig bronchus [ 31]. However, Martin et al have subinsulin sensitivity.…”