Contribution of beta-adrenoceptor subtypes to relaxation of colon and oesophagus and pacemaker activity of ureter in wildtype and beta(3)-adrenoceptor knockout mice
| Autor: | J, Oostendorp, F, Preitner, J, Moffatt, M, Jimenez, J P, Giacobino, P, Molenaar, A J, Kaumann |
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| Rok vydání: | 2000 |
| Předmět: |
Male
Epinephrine Colon Muscle Relaxation Adrenergic beta-Antagonists Mice Inbred Strains Dioxoles In Vitro Techniques Propanolamines Mice Norepinephrine Esophagus Adrenergic beta-2 Receptor Antagonists Receptors Adrenergic beta Animals RNA Messenger Mice Knockout Mice Inbred BALB C Dose-Response Relationship Drug Imidazoles Adrenergic beta-Agonists Adrenergic beta-1 Receptor Antagonists Mice Inbred C57BL Receptors Adrenergic beta-3 Papers Female Receptors Adrenergic beta-2 Receptors Adrenergic beta-1 Ureter |
| Zdroj: | British journal of pharmacology. 130(4) |
| ISSN: | 0007-1188 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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