Effect of guanyl nucleotides on parathyroid hormone-responsive adenylate cyclase in chick kidney.
Both guanosine 5'-triphosphate (GTP) AND 5'-guanylylimidodiphosphate (Gpp(NH)p) activated adenylate cyclase (EC4.6.1.1) in chick kidney plasma membranes. Half-maximal stimulation occurred at 3-1 X 10(-6)M for both agents. The maximum increases in adenylate cyclase activity produced by GTP and Gpp(NH)p were respectively 130 and 720% over basal activity. At the end of a 12 min incubation period GTP concentration was 85% of that originally added in the presence of an ATP-regenerating system but less than 20% in its absence. GTP and guanosine 5'-diphosphate inhibited the activation of adenylate cyclase by Gpp(NH)p, suggesting that they all acted at a common site. Gpp(NH)p facilitated the stimulation of adenylate cyclase activity by bovine parathyroid hormone (BPTH) and by the synthetic amino terminal fragment BPTH (1-34), decreasing the concentrations required for half-maximal enzyme activation by a factor of approximately eight in both cases. This property was not shared by the native nucleotide GTP. Gpp(NH)p rendered active (at certain concentrations) a synthetic parathyroid hormone peptide fragment, BPTH (2-34), which was incapable of Activating adenylate cyclase in the absence of the nucleotide analogue. This suggested that the GTP analogue, in addition to a direct effect upon adenylate cyclase activity, was capable of influencing hormone interaction with the enzyme complex.
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D002462:Cell Membrane / Q000201:enzymology; D002645:Chickens; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D006150:Guanine Nucleotides / Q000494:pharmacology*; D006160:Guanosine Triphosphate / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D010281:Parathyroid Hormone / Q000494:pharmacology*
D006150:Guanine Nucleotides; D010281:Parathyroid Hormone; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D000262:Adenylyl Cyclases