Postjunctional synergism of norepinephrine with ATP and diadenosine tetraphosphate in Guinea pig vas deferens. Role of protein kinase C and Myosin light chain phosphatase.
In isolated guinea pig vas deferens, prior addition of norepinephrine (NE) significantly potentiated the contractile responses to adenosine-5'-triphosphate (ATP) and diadenosine tetraphosphate (AP4A) in a dose-dependent manner up to 240% of the control purine dose. The myosin light chain phosphatase (MLCP) inhibitor cantharidin at a dose of 10 micromol/l caused significant enhancement of ATP at concentrations of 1 and 3 mmol/l by 91 and 95% respectively. Similarly, cantharidin enhanced the contraction to AP4A, 30 and 100 micromol/l by 92 and 100% respectively. Inhibition of protein kinase C (PKC) by the use of chelerythrine (10 micromol/l), incubated at the vas deferens for 60 min, inhibited the NE-induced enhancement of purine-induced contraction. Chelerythrine reversed the NE-ATP and NE-AP4A synergism back close to control ATP and AP4A contraction values respectively. It can be concluded that postjunctional synergism becomes evident not only for adenine mononucleotides and NE but also for diadenosine polyphosphates presented here by AP4A in the guinea pig vas deferens. This synergism involves receptor-mediated activation of PKC and possibly PKC-induced inhibition of MLCP.
Khattab
Mahmoud M
MM
Department of Pharmacology, College of Pharmacy, King Saud University, Riyadh, Kingdom of Saudi Arabia. mahkhattab@yahoo.com
Al-Rawi
Mahmood B
MB
Aleisa
Abdulaziz M
AM
D000255:Adenosine Triphosphate / Q000494:pharmacology*; D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology*; D002193:Cantharidin / Q000494:pharmacology*; D015226:Dinucleoside Phosphates / Q000494:pharmacology*; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006168:Guinea Pigs; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects; D043263:Myosin-Light-Chain Phosphatase / Q000037:antagonists & inhibitors* / Q000502:physiology; D009638:Norepinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D014649:Vas Deferens / Q000187:drug effects
D000470:Alkaloids; D053119:Benzophenanthridines; D015226:Dinucleoside Phosphates; D004791:Enzyme Inhibitors; C020733:diadenosine tetraphosphate; D000255:Adenosine Triphosphate; C016299:chelerythrine; D011493:Protein Kinase C; D043263:Myosin-Light-Chain Phosphatase; D002193:Cantharidin; D009638:Norepinephrine