Effects of ethanol on adenylate cyclase system in the human platelet.
Effects of ethanol (EtOH) on the alpha 2-receptor-coupled adenylate cyclase (AC) of the human platelet were examined. EtOH increased "basal" AC activity in a linear dose dependent manner. In the presence of Gpp(NH)p (2.5 microM), however, the slope of the dose-response curve for EtOH stimulation of AC activity was biphasic. The increase in activity produced by the addition of EtOH concentration between 0 and 100 mM was much sharper than the increase in activity produced by the concentration in excess of 100 mM. EtOH increased the rate of activation of AC by guanine nucleotides and concomitantly decreased the concentration of magnesium required for half-maximal activation of AC. Prostaglandin-E1 (PGE1) alone stimulated AC activity. Clonidine (3 nM-1 microM) diminished the PGE1 (1 microM)-stimulated AC by a maximum of 30%. EtOH did not alter the concentration of clonidine required for half-maximal inhibition of AC. Our results suggest that the sites of EtOH's action can be assigned to the direct action of the catalytic subunit and to the Ns-protein. Our results also indicate a substantial difference in EtOH's action on catecholamine receptor systems coupled in a stimulatory versus inhibitory manner to AC. Stimulation of AC through Ns-protein is potentiated by EtOH, but inhibition of AC through the Ni-protein is little affected by EtOH.
Department of Neuropsychiatry, Sapporo Medical College, Japan.
T
T
Saito
H
H
Ozawa
F
F
Tsuchiya
H
H
Ishizawa
B
B
Tabakoff
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000527:Alprostadil / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000201:enzymology; D003000:Clonidine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D000431:Ethanol / Q000494:pharmacology*; D006801:Humans
D000431:Ethanol; D000262:Adenylyl Cyclases; D000527:Alprostadil; D003000:Clonidine