Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via beta-adrenoceptors
- PMID: 16054622
- DOI: 10.1016/j.ejphar.2005.06.029
Involvement of cyclic AMP-dependent and -independent mechanisms in the relaxation of rat detrusor muscle via beta-adrenoceptors
Abstract
We investigated the cAMP-dependent and -independent mechanisms of relaxation via beta-adrenoceptor in rat detrusor muscle with and without pre-contraction. A microdialysis technique was used to measure detrusor tension and cAMP level on the same detrusor tissue. In non-contracted tissue, isoproterenol, clenbuterol (beta2-adrenoceptor agonist) and FR165101, ((8S)-8-{[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino}-6,7,8,9-tetrahydro-5H-benzocyclohepten-2-yl)oxy]acetic acid hydrochloride (beta3-adrenoceptor agonist) relaxed detrusor muscle and cAMP levels also increased in a concentration dependent manner. SQ22536 (adenylyl cyclase inhibitor) markedly suppressed relaxation, suggesting that beta-adrenoceptor-mediated relaxation may be attributed mainly to cAMP-dependent mechanism. In high K+ pre-contracted tissue, although relaxation advanced in a concentration dependent manner, cAMP production reached a plateau at concentrations of more than 10(-7) M. SQ22536 had only a small inhibitory effect. However, large-conductance, Ca2+-activated K+ (BK(Ca)) channel inhibitors, charybdotoxin and iberiotoxin markedly suppressed relaxation. These results suggest that in addition to cAMP-dependent pathway, BK(Ca) channels are involved in the beta-adrenoceptor agonists-induced relaxation in pre-contracted detrusor muscle.
Similar articles
-
Evidence for the primary role for 4-aminopyridine-sensitive K(v) channels in beta(3)-adrenoceptor-mediated, cyclic AMP-independent relaxations of guinea-pig gastrointestinal smooth muscles.Naunyn Schmiedebergs Arch Pharmacol. 2003 Feb;367(2):193-203. doi: 10.1007/s00210-002-0658-3. Epub 2003 Jan 14. Naunyn Schmiedebergs Arch Pharmacol. 2003. PMID: 12595962
-
Does cyclic AMP mediate rat urinary bladder relaxation by isoproterenol?J Pharmacol Exp Ther. 2005 Apr;313(1):260-7. doi: 10.1124/jpet.104.077768. Epub 2004 Dec 2. J Pharmacol Exp Ther. 2005. PMID: 15576470
-
Expression and possible functional role of the beta3-adrenoceptor in human and rat detrusor muscle.J Urol. 1999 Feb;161(2):680-5. J Urol. 1999. PMID: 9915482
-
New insights into beta-adrenoceptors in smooth muscle: distribution of receptor subtypes and molecular mechanisms triggering muscle relaxation.Clin Exp Pharmacol Physiol. 2005 Jul;32(7):503-14. doi: 10.1111/j.1440-1681.2005.04222.x. Clin Exp Pharmacol Physiol. 2005. PMID: 16026507 Review.
-
Beta-adrenoceptors, cAMP and airway smooth muscle relaxation: challenges to the dogma.Trends Pharmacol Sci. 1994 Oct;15(10):370-4. doi: 10.1016/0165-6147(94)90157-0. Trends Pharmacol Sci. 1994. PMID: 7809952 Review.
Cited by
-
Inhibition of phosphodiesterases relaxes detrusor smooth muscle via activation of the large-conductance voltage- and Ca²⁺-activated K⁺ channel.Am J Physiol Cell Physiol. 2012 May 1;302(9):C1361-70. doi: 10.1152/ajpcell.00432.2011. Epub 2012 Feb 8. Am J Physiol Cell Physiol. 2012. PMID: 22322973 Free PMC article.
-
Desensitization of cAMP Accumulation via Human β3-Adrenoceptors Expressed in Human Embryonic Kidney Cells by Full, Partial, and Biased Agonists.Front Pharmacol. 2019 Jun 7;10:596. doi: 10.3389/fphar.2019.00596. eCollection 2019. Front Pharmacol. 2019. PMID: 31263412 Free PMC article.
-
In vitro and in vivo pharmacological profile of the selective β3-adrenoceptor agonist mirabegron in rats.Naunyn Schmiedebergs Arch Pharmacol. 2013 Mar;386(3):247-53. doi: 10.1007/s00210-012-0821-4. Epub 2012 Dec 14. Naunyn Schmiedebergs Arch Pharmacol. 2013. PMID: 23239087
-
Signal transduction underlying the control of urinary bladder smooth muscle tone by muscarinic receptors and beta-adrenoceptors.Naunyn Schmiedebergs Arch Pharmacol. 2008 Jun;377(4-6):449-62. doi: 10.1007/s00210-007-0208-0. Epub 2007 Dec 4. Naunyn Schmiedebergs Arch Pharmacol. 2008. PMID: 18060543 Free PMC article. Review.
-
β-Adrenoceptor-mediated differences in transverse and longitudinal strips from the rat detrusor.Int Urol Nephrol. 2011 Mar;43(1):99-107. doi: 10.1007/s11255-010-9759-y. Epub 2010 May 21. Int Urol Nephrol. 2011. PMID: 20490667
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Miscellaneous
