Neuropeptide Y inhibits cholinergic transmission in the isolated guinea pig colon: mediation through alpha-adrenergic receptors.

Neuropeptide Y, a member of the pancreatic polypeptide family, caused dose-dependent relaxation of guinea pig colon longitudinal muscle. This inhibitory effect was unaffected by hexamethonium but was abolished by atropine and tetrodotoxin, suggesting that neuropeptide Y is acting via postganglionic cholinergic neurons. Studies utilizing alpha-adrenergic and dopamine receptor antagonists revealed that neuropeptide Y-mediated relaxation was blocked only by the alpha 2 antagonist yohimbine. Neuropeptide Y also antagonized muscle response to electric field stimulation that was reversed by yohimbine. Additional studies with muscle slices incubated with [3H]norepinephrine or [3H]choline showed that neuropeptide Y stimulated norepinephrine release from sympathetic nerves, which, in turn, inhibited the release of acetylcholine via alpha 2 receptors located on postganglionic nerves. This pathway provides a mechanism for neuropeptide modulation of classical neurotransmitter function.