AJP - Gastrointestinal and Liver Physiology, Vol 251, Issue 6 794-G803, Copyright © 1986 by American Physiological Society
Cyclic nucleotide-dependent protein kinases in the lower esophageal sphincter
C. A. Miller, M. S. Barnette, H. S. Ormsbee 3rd and T. J. Torphy
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.
