Negative modulation of L-type Ca2+ channels via beta-adrenoceptor stimulation in guinea-pig detrusor smooth muscle cells.
beta-Adrenergic stimulation enhances the activity of L-type Ca(2+) channels through mechanisms mediated by adenosine 3'5'-cyclic monophosphate (cAMP) and protein kinase A in cardiac myocytes. However, in smooth muscle cells, the effect of beta-adrenoceptor stimulation on the L-type Ca(2+) channel activity has been controversial, and the exact mechanism is still unclear. The present study was aimed at elucidating the effect of beta-adrenergic stimulation upon the activity of L-type Ca(2+) channels in guinea-pig detrusor smooth muscle cells. Isoproterenol (0.1-1 microM) inhibited Ba(2+) currents through L-type Ca(2+) channels (I(Ba)). Isoproterenol (0.1 microM) shifted the steady-state inactivation curve to negative voltages by 11 mV without affecting activation curves. The stimulation of cAMP-mediated signal transduction pathway by forskolin, 8-bromoadenosine 3'5'-cyclic monophosphate (8-Br-cAMP), or the intracellular application of cAMP also mimicked the effects of isoproterenol on I(Ba), which was blocked by the inhibition of protein kinase A. These results indicate that, in detrusor smooth muscles, the stimulation of beta-adrenoceptors exerts negative modulation of L-type Ca(2+) channels via cAMP/protein kinase A-dependent mechanism.
Kobayashi
Hiroyuki
H
Laboratory of Pharmacology and Toxicology, Graduate School of Pharmaceutical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi, Fukuoka 812-8582, Japan.
Miwa
Takashi
T
Nagao
Taku
T
Adachi-Akahane
Satomi
S
D000818:Animals; D020746:Calcium Channels, L-Type / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006168:Guinea Pigs; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D001743:Urinary Bladder / Q000187:drug effects / Q000378:metabolism
D020746:Calcium Channels, L-Type; D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D007545:Isoproterenol