Excitatory and inhibitory effects of norepinephrine on myenteric neurons of the guinea-pig gastric corpus.

The effects of norepinephrine on the electrical and synaptic behaviour of gastric myenteric neurons were investigated in vitro by using conventional intracellular recording methods. Application of norepinephrine (0.1-10 microM) evoked an excitatory effect in 40% of all cells tested. Excitation consisted of a depolarization of the membrane potential associated with increased spike discharge. Phentolamine or prazosin reversibly abolished and (-)phenylephrine mimicked the excitatory norepinephrine response. Yohimbine and clonidine had no effect. Focal electrical stimulation of interganglionic fibre tracts evoked fast excitatory postsynaptic potentials (fEPSPs) in all neurons. Only a minority of these fEPSPs were blocked by norepinephrine. However, fEPSPs evoked by stimulating presumably extrinsic nerves were always totally blocked by norepinephrine. The inhibitory effect of norepinephrine on fEPSPs could be reversed by phentolamine and yohimbine and mimicked by clonidine. Prazosin and phenylephrine had no effect. Isoproterenol and propranolol modified neither the excitatory nor the inhibitory effects. The results indicate that the excitatory effects of norepinephrine on gastric myenteric neurons are mediated by postsynaptic alpha 1 receptors, whereas the inhibitory effects are mediated by presynaptic alpha 2 receptors, which are located presumably on vagal extrinsic nerves. There was no evidence for beta-receptor-mediated effects in gastric myenteric neurons.