Cyclic nucleotide-dependent protein kinases in the lower esophageal sphincter.
The characteristics and regulation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent and guanosine 3',5'-cyclic monophosphate (cGMP)-dependent protein kinases (PKs) in opossum, canine, and human lower esophageal sphincter (LES) were investigated. As measured by the incorporation of 32P from [gamma-32P]adenosine 5'-triphosphate (ATP) into histone, LES homogenates from all three species contained three distinct types of PK: cAMP-dependent PK, cGMP-dependent PK, and cyclic nucleotide-independent PK. In all three species, cAMP-dependent PK comprised approximately 80%, cGMP-dependent PK comprised approximately 10%, and cyclic nucleotide-independent PK comprised approximately 10% of the total PK activity in the LES. Diethylaminoethyl-sepharose column chromatography of the supernatant fraction of opossum LES homogenates revealed that of the total cAMP-dependent PK, 10% was Type I and 90% was Type II. In contrast, equal amounts of Type I and Type II cAMP-dependent PK were present in both the human and canine LES. Isoproterenol-induced relaxation of the isolated opossum LES was accompanied by an increase in cAMP content and an activation of cAMP-dependent PK. The results of this study support the proposal that cyclic nucleotides and cyclic nucleotide-dependent PKs regulate LES tone.
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D000242:Cyclic AMP / Q000494:pharmacology; D006152:Cyclic GMP / Q000494:pharmacology; D004285:Dogs; D004947:Esophagus / Q000201:enzymology*; D005260:Female; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D009893:Opossums; D011494:Protein Kinases / Q000378:metabolism*
D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D011494:Protein Kinases; D006152:Cyclic GMP; D007545:Isoproterenol