Philyppov I. Metabotropic regulation of the purinergic synaptic inhibition in visceral smooth muscles

The present study is devoted to the investigation of the separate stages of the signaling system, which underlines purinergic inhibition of visceral smooth muscles. Using sucrose-gap and tensometric technique it was investigated the role of intracellular messenger in the mechanisms of nonadrenergic inhibitory junction potentials (IJP) generation and ATP-induced inhibition. It was shown partial suppression of IJP by the phospholipase C blocker U 73122 that provide the existence of phospholipase C-dependent and phospholipase C-independent pathways involved in generation of the first component of IJP and ATP hyperpolarization. In our study we first found differences between cellular mechanisms underlying ATP-inhibition of smooth muscles under conditions of selective activation of either muscarinic M2 or M3 cholinoceptors and the mechanisms underlying the relaxing action of inhibitory neurotransmitters under conditions of combined synergistic activation of cholinoceptors of both the above-mentioned subtypes. Selective blockings of either M2 or M3 cholinoceptors are accompanied by a complete loss of the ability of the blocker of ІР3 receptors to suppress ATP-induced relaxation of smooth muscles in the state of CCh-induced contraction. It can be hypothesized that, under conditions of selective pre-activation of M2 or M3 cholinoceptors, the mechanisms of intracellular signaling mediating the inhibition are modified. The ІР3-dependent pathway that determines purinergic inhibition of smooth muscles is switched off, and the inhibitory action of neurotransmitters is realized under such conditions through the phospholipase C- and ІР3-independent pathways.