Vn. Mutafovayambolieva et Kd. Keef, ADENOSINE-INDUCED HYPERPOLARIZATION IN GUINEA-PIG CORONARY-ARTERY INVOLVES A(2B) RECEPTORS AND K-ATP CHANNELS, American journal of physiology. Heart and circulatory physiology, 42(6), 1997, pp. 2687-2695
The role of P-1 purinoceptor subtypes, the adenylyl cyclase (AC) pathw
ay, and ATP-sensitive K+ (K-ATP) channels in adenosine (Ado)-induced m
embrane hyperpolarization was investigated in isolated segments of the
guinea pig coronary artery using conventional microelectrode techniqu
es. Ado (1-100 mu M) elicited concentration-dependent hyperpolarizatio
n (half-maximal effective concentration 7.5 +/- 0.5 mu M) that average
d 28.6 +/- 2.9 mV at 100 mu M Ado. The A(1) selective agonist N-G-cycl
opentyladenosine (CPA), the A(1)/A(2) agonist 2-chloroadenosine, and t
he A(2a)/A(2b) agonist 5-(N-ethylcarboxamido)adenosine (NECA) each ind
uced glibenclamide (3 mu M)sensitive hyperpolarization at 10 mu M. How
ever, the selective A(2a)-receptor agonists CGS-21680 and dimethoxyphe
nyl)-2-(2-methoxyphenyl]ethyladenosine (10 mu M each) were without eff
ect. Responses to CPA and NECA were significantly reduced by the AC in
hibitor SQ-22,536 (100 mu M). Activation of the AC-adenosine 3',5'-cyc
lic monophosphate (cAMP)-protein kinase A (PKA) pathway by four additi
onal methods, i.e., 1) forskolin (0.3-1 mu M), 2) isoproterenol (0.1-1
mu M), 3) combined milrinone (0.4 mu M) and rolipram (30 mu M), and 4
) combined N-6-phenyladenosine 3',5'-monophosphate, 8-(6-aminohexyl)am
inoadenosine 3',5'-cyclic monophosphate, and the Sp-isomer of 5,6-dich
loro-1-D-ribofuranosylbenzimid azole-3',5'-cyclic monophosphothioate (
100 mu M each), also gave rise to glibenclamide-sensitive hyperpolariz
ation. These results suggest that stimulation of A(2b) receptors coupl
ed to AC represents the predominant mechanism by which Ado elicits hyp
erpolarization in this vessel. The ensuing increase in cAMP activates
PKA, which then increases the activity of K-ATP channels. Our results
further suggest that K-ATP channels are an important target for numero
us pathways that raise cAMP levels in the coronary artery.