Cyclic AMP and cyclic GMP relax phorbol ester-induced contractions of rat aorta by different mechanisms.
This study was designed to test the hypothesis that 8-Br-cAMP and 8-Br-cGMP dependent relaxation of phorbol dibutyrate stimulated contractions of intact rat aorta are independent of changes in the level of myosin light chain phosphorylation. Phorbol dibutyrate stimulated contraction with a concomitant increase in myosin light chain phosphorylation in normal tissues and without an increase in myosin light chain phosphorylation in calcium-depleted tissues. Phorbol dibutyrate stimulated contractions in normal CaCl2-containing physiological salt solution were relaxed in a concentration-dependent manner by 8-Br-cAMP and 8-Br-cGMP. Phorbol dibutyrate-induced contractions in the absence of Ca2+ were only relaxed by 8-Br-cGMP; 8-Br-cAMP had no effect. The relaxation induced by 8-Br-cGMP was associated with a decrease in myosin light chain phosphorylation suggesting that cGMP-dependent protein kinase may alter the activity of either the myosin light chain kinase or phosphatase. The relaxation induced by 8-Br-cAMP was not associated with a decrease in phosphorylation suggesting that cAMP-dependent protein kinase may uncouple myosin light chain phosphorylation from force.
Ahn
H Y
HY
Department of Pharmacology, College of Medicine, Chungbuk National University, Cheongju, South Korea.
Chang
K C
KC
Chung
M H
MH
Kim
M S
MS
Moreland
R S
RS
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000502:physiology; D000242:Cyclic AMP / Q000502:physiology; D006152:Cyclic GMP / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000502:physiology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000502:physiology; D018994:Myosin Light Chains / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013268:Stimulation, Chemical
D018994:Myosin Light Chains; D015124:8-Bromo Cyclic Adenosine Monophosphate; C016276:8-bromocyclic GMP; D015240:Phorbol 12,13-Dibutyrate; D000242:Cyclic AMP; D011493:Protein Kinase C; D006152:Cyclic GMP