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 (AP(4)A) 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 mu mol/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 AP(4)A, 30 and 100 mu mol/l by 92 and 100% respectively. Inhibition of protein kinase C (PKC) by the use of chelerythrine (10 mu mol/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-AP(4)A synergism back close to control ATP and AP(4)A 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 AP(4)A in the guinea pig vas deferens. This synergism involves receptor-mediated activation of PKC and possibly PKC-induced inhibition of MLCP.