Mechanisms of cAMP-mediated relaxation of distal circular muscle in rabbit colon.
Photolytic release of free adenosine 3',5'-cyclic monophosphate (cAMP) from its caged form was used to evaluate the physiological role of several proposed mechanisms of cAMP-mediated relaxation of circular smooth muscle in the distal rabbit colon. Photolysis of caged cAMP produced a rapid relaxation of bethanechol-contracted distal circular muscle strips that was dependent on ultraviolet exposure time. An increase in release of free cAMP, associated with increased ultraviolet exposure, was confirmed with high-performance liquid chromatography. Vanadate (an ATPase inhibitor) (3 mM) caused a 48% decrease in cAMP-mediated relaxation, while ouabain and a zero K+ bath solution failed to affect relaxation. cAMP-mediated relaxation of KCl-contracted strips was significantly less effective than that of bethanechol-contracted strips. Although this finding suggested that cAMP-mediated relaxation may involve K+ channel modulation, specific (glibenclamide, charybdotoxin) and nonspecific (TEA) K+ channel blockade failed to affect cAMP-mediated relaxation of bethanechol-contracted strips. The photolytic release of cAMP failed to relax Ca(2+)-contracted saponin skinned muscle strips. These studies suggest 1) modulation of Ca2+ pumps plays an important role in this model of relaxation of distal colonic circular muscle in the rabbit colon, 2) modulation of the Na+ pump or sarcolemmal K+ channels may not play an important physiological role in relaxation induced by a rapid rise in intracellular cAMP, and 3) cAMP does not seem to have a significant physiological effect on the Ca2+ sensitivity contractile apparatus.
Willenbucher
R F
RF
Department of Medicine, Harbor-University of California, Los Angeles, Medical Center, Torrance 90502.
Xie
Y N
YN
Eysselein
V E
VE
Snape
W J
WJ
D000818:Animals; D018723:Bethanechol; D001626:Bethanechol Compounds / Q000494:pharmacology; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D007537:Isometric Contraction / Q000502:physiology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects* / Q000378:metabolism; D010042:Ouabain / Q000494:pharmacology; D010782:Photolysis; D011188:Potassium / Q000494:pharmacology; D011817:Rabbits; D013779:Tetrodotoxin / Q000494:pharmacology; D014638:Vanadates / Q000494:pharmacology
D001626:Bethanechol Compounds; D018723:Bethanechol; D014638:Vanadates; D013779:Tetrodotoxin; D010042:Ouabain; D000242:Cyclic AMP; D011188:Potassium