beta-adrenoceptor mediated responses in rat pulmonary artery: putative role of TASK-1 related K channels.
The effect of isoprenaline on tone, cyclic adenosine 3':5' monophosphate (cAMP), and smooth muscle membrane potential (E ( m )) were assessed in rat isolated pulmonary arteries. N(omega)-nitro-L-arginine methyl ester (10.0 microM) or removal of endothelium partially inhibited relaxant responses to isoprenaline, but glibenclamide (10.0 microM) and indomethacin (10.0 microM) did not. While Rp-8-Br-cAMP (30.0 microM), tetraethylammonium (0.3 & 1.0 mM), 4-aminopyridine (100 microM), anandamide (10.0 microM), charybdotoxin (0.1 microM), ouabain (100 microM), and barium chloride (100 microM), incompletely blocked relaxation to isoprenaline, cyclopiazonic acid (1.0 microM), apamin (3.0 microM) and zinc acetate (300 microM) were without effect. Increasing extracellular K(+) ([K(+)](e)) inhibited relaxant responses to isoprenaline, completely abolishing the response at 30 mM [K+](e). Vasorelaxant effects of isoprenaline were significantly attenuated in buffer pH 6.4, and concomitant presence of Rp-8-Br-cAMP (30.0 microM) in pH 6.4 produced significant additive inhibition when compared to pH 6.4 without Rp-8-Br-cAMP. Isoprenaline increased cAMP turnover (1.55+/-0.24 fold; mean +/- SEM), which was inhibited by propranolol (1.0 microM). Resting E ( m ) of smooth muscle cells was -63.0+/-0.50 mV, and isoprenaline (1.0 microM) produced hyperpolarisation (-73.3+/-0.80 mV). While glibenclamide failed to affect isoprenaline-induced hyperpolarisation, ICI 118,551 (1.0 microM), anandamide or buffer pH 6.4 prevented it, and barium chloride and oubain combined caused partial inhibition. Isoprenaline-mediated relaxation seems to arise from several processes, including the generation of nitric oxide, the cAMP-cascade and, more importantly, a hyperpolarisation that is not due to activation of ATP-sensitive K channels but possibly of two-pore domain K channels of the TASK family.
Bieger
Detlef
D
Division of Basic Medical Sciences, Faculty of Medicine, Memorial University of Newfoundland, St. John's, NL, Canada.
Parai
Kakoli
K
Ford
Carol Ann
CA
Tabrizchi
Reza
R
D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*
D009419:Nerve Tissue Proteins; D024683:Potassium Channels, Tandem Pore Domain; D011943:Receptors, Adrenergic, beta; C420132:potassium channel subfamily K member 3; D000242:Cyclic AMP; D007545:Isoproterenol