Role of phospholipids in coupling of adenosine and dopamine receptors to striatal adenylate cyclase.
Treatment of striatal washed particles with phospholipase A(2) or C abolished the activation of adenylate cyclase by dopamine but not by N(16)-phenylisopropyl adenosine (PIA). The inhibition of dopamine-sensitive cyclase was dependent on Ca2+ and increased with time and phospholipase concentration. F(-)-sensitive cyclase was not affected by phospholipase A(2) treatment, but was enhanced by phospholipase C treatment. Phospholipase D did not affect basal, PIA, dopamine, or F(-)-sensitive cyclase activities. The observed effects of phospholipase A(2) were not due to either the detergent effect of lysophospholipids or to contaminating proteases. Dopamine-sensitive cyclase, inactivated by pretreatment with phospholipase A(2), was restored by asolectin (a soybean mixed phospholipid), phosphatidylcholine, phosphatidylethanolamine, or phosphatidylserine, but not by phosphatidylinositol. Phosphatidylserine and phosphatidylcholine were equipotent in restoring dopamine-sensitive activity. Lubrol-PX, a nonionic detergent, abolished completely the dopamine-sensitive cyclase activity, whereas PIA-sensitive activity was slightly inhibited. In contrast, digitonin inhibited dopamine- and PIA-sensitive cyclase activity in a parallel fashion. Lubrol-PX released some adenylate cyclase into a 16,000 x g supernatant fraction that was stimulated by PIA but not by dopamine. Removal of most of the free detergent by Bio-bead SM 2 enhanced stimulation by PIA but did not restore sensitive cyclase. The data suggest that the requirement for phospholipids for the coupling of dopamine and adenosine receptors to the striatal adenylate cyclase may be different and that the adenosine receptors may be more tightly coupled to the enzyme than are dopamine receptors.
D000241:Adenosine / Q000031:analogs & derivatives*; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D003342:Corpus Striatum / Q000201:enzymology*; D004298:Dopamine / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D008297:Male; D010660:Phenylisopropyladenosine / Q000494:pharmacology*; D010713:Phosphatidylcholines / Q000494:pharmacology; D010714:Phosphatidylethanolamines / Q000494:pharmacology; D010718:Phosphatidylserines / Q000494:pharmacology; D010741:Phospholipases A / Q000494:pharmacology; D010743:Phospholipids / Q000494:pharmacology*; D000077423:Polidocanol; D011092:Polyethylene Glycols / Q000494:pharmacology; D051381:Rats; D011956:Receptors, Cell Surface / Q000378:metabolism; D011954:Receptors, Dopamine / Q000378:metabolism; D011983:Receptors, Purinergic; D010738:Type C Phospholipases / Q000494:pharmacology
D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010718:Phosphatidylserines; D010743:Phospholipids; D011956:Receptors, Cell Surface; D011954:Receptors, Dopamine; D011983:Receptors, Purinergic; D000077423:Polidocanol; D010660:Phenylisopropyladenosine; D011092:Polyethylene Glycols; C024990:asolectin; D010741:Phospholipases A; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D000241:Adenosine; D004298:Dopamine