The dopamine-1 agonist, SKF 82526, stimulates phospholipase-C activity independent of adenylate cyclase.
Dopamine-1 (DA-1) receptors have been found in renal tubular membranes which stimulate both adenylate cyclase and phospholipase-C activity. In renal cortical plasma membrane preparations the DA-1 agonist SKF 82526, forskolin and NaF stimulated adenylate cyclase activity. 2',5'-dideoxyadenosine inhibited basal and DA-1 agonist stimulated adenylate cyclase activity. Forskolin, NaF, dibutyryl-cyclic AMP and 2',5'-dideoxyadenosine had no effect on basal or DA-1 agonist stimulated phospholipase-C activity in these membranes. These studies indicate that DA-1 agonist stimulates adenylate cyclase and phospholipase-C activities independently. Phospholipase-C activity was also increased by the nonhydrolyzable GTP analog, guanosine-5'-O-(3-thiophosphate). When DA-1 agonist and guanosine-5'-O-(3-thiophosphate) were added together there was a slight but significant increase in phospholipase-C activity. This increase was inhibited in the presence of guanosine-5'-O-(2-thiodiphosphate). DA-1 stimulated phospholipase-C activity was found to be insensitive to both cholera and pertussis toxins. The present studies indicate a cyclic AMP independent transduction pathway for DA-1 receptor mediated through a guanine nucleotide regulatory protein associated phospholipase-C.
Felder
C C
CC
Section on Pharmacology, National Institute of Mental Health, Bethesda, Maryland.
Jose
P A
PA
Axelrod
J
J
D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D001552:Benzazepines / Q000494:pharmacology*; D003994:Bucladesine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D016048:Dideoxyadenosine / Q000031:analogs & derivatives*; D015224:Dideoxynucleosides / Q000494:pharmacology; D015259:Dopamine Agents / Q000494:pharmacology*; D018818:Fenoldopam; D019204:GTP-Binding Proteins / Q000502:physiology; D006150:Guanine Nucleotides / Q000494:pharmacology; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects*; D017447:Receptors, Dopamine D1; D012969:Sodium Fluoride / Q000494:pharmacology; D010738:Type C Phospholipases / Q000032:analysis*
D001552:Benzazepines; D015224:Dideoxynucleosides; D015259:Dopamine Agents; D006150:Guanine Nucleotides; D011954:Receptors, Dopamine; D017447:Receptors, Dopamine D1; D005576:Colforsin; D016048:Dideoxyadenosine; D003994:Bucladesine; D012969:Sodium Fluoride; C021008:2',5'-dideoxyadenosine; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; D018818:Fenoldopam