Regulation of inositol 1,4,5-trisphosphate-induced Ca2+ release. II. Effect of cAMP-dependent protein kinase.
The effect of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase (PKA) on Ca2+ loading, inositol 1,4,5-trisphosphate (IP3)-induced Ca2+ release, and [3H]IP3 binding of canine cerebellar membrane fractions was investigated. PKA in the presence of cAMP and the catalytic subunit of PKA did not change Ca2+ loading yet increased the extent of IP3-induced Ca2+ release by approximately 35%. Hill plot analysis indicated that the catalytic subunit of PKA increased the apparent Michaelis constant of IP3-induced Ca2+ release twofold, from 0.3 to 0.7 microM IP3. The protein kinase inhibitor reversed these changes. cAMP affected neither Ca2+ loading nor IP3-induced Ca2+ release. The catalytic subunit of PKA did not appreciably affect the maximum binding and dissociation constant of [3H]IP3 binding, as judged by Scatchard analysis. Thus the catalytic subunit of PKA influences the opening of Ca2+ channels by IP3 without interfering with the binding of IP3 to its receptor sites.
Volpe
P
P
Department of Physiology and Biophysics, University of Texas Medical Branch, Galveston 77550.
Alderson-Lang
B H
BH
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism*; D000242:Cyclic AMP / Q000494:pharmacology; D004285:Dogs; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism / Q000494:pharmacology*; D007700:Kinetics; D046911:Macromolecular Substances; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D011494:Protein Kinases / Q000378:metabolism* / Q000494:pharmacology
D046911:Macromolecular Substances; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D002118:Calcium