CA2+ DEPENDENCE OF THE RESPONSE OF 3 ADENOSINE TYPE RECEPTORS IN RAT HEPATOCYTES

The effect of three different receptor-specific adenosine agonists on the rate of ureagenesis by isolated rat hepatocytes and the dependence on the external free Ca2+ concentration ([Ca2+](e)) were investigated . In the presence of high [Ca2+](e) all adenosine receptor agonists in creased ureagenesis to similar levels. However, with low [Ca2+](e) the effects of each agonist varied as follows: (i) the adenosine A(1) rec eptor agonist, 2-chloro-N-6-cyclopentyl-adenosine, increased ureagenes is depending partially on [Ca2+](e), (ii) the adenosine receptor A(2) agonist, 2-p-(-2-carboxy-ethyl) phenethylamino-5'-N-ethylcarboxyamido adenosine hydrochloride, increased ureagenesis independently of [Ca2+] (e) and (iii) in contrast, the adenosine receptor A(3) agonist N-6-2-( -4-aminophenyl) ethyladenosine, increased ureagenesis only in the pres ence of high [Ca2+](e). The adenosine receptor A(1) antagonist, 1-ally l-3,7-dimethyl-8-phenyl xanthine, inhibited the effect of the adenosin e receptor A(1) agonist on ureagenesis, but not the effect of the aden osine A(2) or A(3) receptor agonists. The adenosine A(2) receptor anta gonist, 3,7-dimethyl-1-propargylxanthine, inhibited only the effect of the adenosine A(2) receptor agonist. Thus, in addition to A(1) and A( 2) type adenosine receptors, rat hepatocytes possess an A(3)-like aden osine receptor which responds to the addition of an adenosine A(3) ago nist by accelerating ureagenesis a [Ca2+](e) dependent manner. Moreove r, it was observed that in the presence of extracellular Ca2+ each ago nist increased [Ca2+](i) and this effect was inhibited by the appropri ate specific antagonist. (C) 1997 Elsevier Science B.V.