Contribution of β-adrenoceptor subtypes to relaxation of colon and oesophagus and pacemaker activity of ureter in wildtype and β3 -adrenoceptor knockout mice
- 1 June 2000
- journal article
- Published by Wiley in British Journal of Pharmacology
- Vol. 130 (4) , 747-758
- https://doi.org/10.1038/sj.bjp.0703365
Abstract
The smooth muscle relaxant responses to the mixed beta(3)-, putative beta(4)-adrenoceptor agonist, (-)-CGP 12177 in rat colon are partially resistant to blockade by the beta(3)-adrenoceptor antagonist SR59230A suggesting involvement of beta(3)- and putative beta(4)-adrenoceptors. We now investigated the function of the putative beta(4)-adrenoceptor and other beta-adrenoceptor subtypes in the colon, oesophagus and ureter of wildtype (WT) and beta(3)-adrenoceptor knockout (beta(3)KO) mice. (-)-Noradrenaline and (-)-adrenaline relaxed KCl (30 mM)-precontracted colon mostly through beta(1)-and beta(3)-adrenoceptors to a similar extent and to a minor extent through beta(2)-adrenoceptors. In colon from beta(3)KO mice, (-)-noradrenaline was as potent as in WT mice but the effects were mediated entirely through beta(1)-adrenoceptors. (-)-CGP 12177 relaxed colon from beta(3)KO mice with 2 fold greater potency than in WT mice. The maintenance of potency for (-)-noradrenaline and increase for (-)-CGP 12177 indicate compensatory increases in beta(1)- and putative beta(4)-adrenoceptor function in beta(3)KO mice. In oesophagi precontracted with 1 microM carbachol, (-)-noradrenaline caused relaxation mainly through beta(1)-and beta(3)-adrenoceptors. (-)-CGP 12177 (2 microM) relaxed oesophagi from WT by 61.4+/-5.1% and beta(3)KO by 67.3+/-10.1% of the (-)-isoprenaline-evoked relaxation, consistent with mediation through putative beta(4)-adrenoceptors. In ureter, (-)-CGP 12177 (2 microM) reduced pacemaker activity by 31.1+/-2.3% in WT and 31.3+/-7. 5% in beta(3)KO, consistent with mediation through putative beta(4)-adrenoceptors. Relaxation of mouse colon and oesophagus by catecholamines are mediated through beta(1)- and beta(3)-adrenoceptors in WT. The putative beta(4)-adrenoceptor, which presumably is an atypical state of the beta(1)-adrenoceptor, mediates the effects of (-)-CGP 12177 in colon, oesophagus and ureter.Keywords
This publication has 38 references indexed in Scilit:
- Putative β4‐adrenoceptors in rat ventricle mediate increases in contractile force and cell Ca2+: comparison with atrial receptors and relationship to (−)‐[3H]‐CGP 12177 bindingBritish Journal of Pharmacology, 1999
- Action potential shortening through the putative β4‐adrenoceptor in ferret ventricle: comparison with β1‐ and β2‐adrenoceptor‐mediated effectsBritish Journal of Pharmacology, 1998
- Metabolic response to various β‐adrenoceptor agonists in β3‐adrenoceptor knockout mice: Evidence for a new β‐adrenergic receptor in brown adipose tissueBritish Journal of Pharmacology, 1998
- Validity of (−)‐[3H]‐CGP 12177A as a radioligand for the ‘putative β4‐adrenoceptor’ in rat atriumBritish Journal of Pharmacology, 1998
- Lipolytic effects of conventional β3‐adrenoceptor agonists and of CGP 12,177 in rat and human fat cells: preliminary pharmacological evidence for a putative β4‐adrenoceptorBritish Journal of Pharmacology, 1997
- Targeted gene disruption reveals a leptin-independent role for the mouse beta3-adrenoceptor in the regulation of body composition.Journal of Clinical Investigation, 1997
- Four β-adrenoceptor subtypes in the mammalian heartPublished by Elsevier ,1997
- Effects of (−)‐RO363 at human atrial β‐adrenoceptor subtypes, the human cloned β3‐adrenoceptor and rodent intestinal β3‐adrenoceptorsBritish Journal of Pharmacology, 1997
- Anomalous Behavior of CGP 12177A ON β2-Adrenergic ReceptorsJournal of Receptors and Signal Transduction, 1996
- Is there a third heart β-adrenoceptor?Trends in Pharmacological Sciences, 1989