ADENOSINE-MEDIATED RELAXATION AND ACTIVATION OF CYCLIC AMP-DEPENDENT PROTEIN-KINASE IN CORONARY ARTERIAL SMOOTH-MUSCLE

  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (2) , 342-347
Abstract
Conflicting evidence regarding the participation of cAMP in adenosine-induced relaxation of the coronary vasculature. Because the mechanism of action of cAMP is thought to involve activation of its dependent protein kinase, whether cytosolic cAMP protein kinase was activated in response to adenosine stimulating and if such activation was correlated to the extent of relaxation in intact coronary arterial strips were determined. Adenosine produced increases in cAMP protein kinase activity in both main trunk and branch circumflex bovine arterial strips. Both the relaxant and kinase effects were greater in branch strips. Concentration and time-dependent increases in adenosine-induced relaxation of contracted branch strips were tightly coupled to concomitant increases in cAMP protein kinase activity (r = 0.93). This increase in kinase activity was ascribable to the cAMP-dependent kinase, as the specific inhibitor of the cAMP protein kinase attenuated these increases. Relaxation produced by sodium nitroprusside was associated with an increase in a cAMP-independent kinase. Cumulative dose-response curves (10-7 to 10-3 M) for relaxation by adenosine and 9 of its analogs [including 1-methyladenosine, adenosine, N''-oxide, 6-methoxypurine, riboside, N6-methyladenosine, 2''-deoxyadenosine, 3''-deoxyadenosine and isopropylidene adenosine-5''-monoacetate] showed that all agents were more effective in branch strips. Adenine-9-.beta.-D-arabinofuranoside, the least potent analog, did not produce relaxation or increase kinase activity. 2-Chloroadenosine, the most effective relaxant analog, also increased cAMP protein kinase activity. Adenosine-induced relaxation may involve cAMP and activation of cAMP protein kinase coronary arterial smooth muscle.

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