Inhibitory effects of NPY on ganglionic transmission in myenteric neuronesof the guinea-pig descending colon

Intracellular recordings were made from myenteric neurones of the guinea-pi g descending colon. Neuropeptide Y (NPY) and related pancreatic polypeptide s were applied by superfusion and the effects upon the amplitude of fast ex citatory synaptic potentials (ESPs) and the ratio of paired fast ESPs evoke d by stimulation of internodal fibre tracts were noted. NPY produced a conc entration-dependent inhibition in fast ESP amplitude in the majority of neu rones (17/21) with a calculated IC50 value of 7 nM; in some neurones this i nhibition was mediated via the local release of noradrenaline. Peptide YY ( PYY) (eight out of 11 neurones; IC50 = 1 nM), NPY(3-36) (three out of three neurones) and [Leu(31), Pro(34)]NPY (four out of five neurones) also decre ased the amplitude of fast ESPs. The effects of two or more pancreatic poly peptides or analogues an fast synaptic transmission were compared directly in six neurones; the apparent relative potency of agonists suggested the in volvement of Y-2-receptors and at least one other Y-receptor type. In the a bsence of any direct postsynaptic effects of pancreatic polypeptides on the active or passive properties of myenteric neurones, or on their sensitivit y to ionophoretically applied acetylcholine, inhibition of-fast ganglionic transmission was presumed to be presynaptic in origin. It is concluded that , in addition to their previously described depressant actions on neuro-eff ector transmission to colonic smooth muscle, pancreatic polypeptides can ex ert powerful inhibitory effects on myenteric neurones of the descending col on.