VIP as a possible neurotransmitter of non-cholinergic non-adrenergic inhibitory neurones

Many peripheral autonomic nerves are neither cholinergic nor adrenergic. Such nerves are widely distributed in the gastrointestinal, urogenital and respiratory tracts, and in blood vessels. The nature of their neurotransmitter is not known. We have previously reported that vasoactive intestinal polypeptide (VIP) is a potent inhibitor of opossum lower oesophageal sphincter (LOS) and that its inhibitory effect is exerted directly on the sphincter muscle. Subsequent studies have confirmed the inhibitory effect of VIP on LOS in other species. Recently, very high tissue levels of VIP have been reported in the LOS and other gastrointestinal sphincters. Furthermore, VIP has been localized to intramural neurones and is released upon electrical stimulation of the vagus nerve. We report here that immunoantagonism of VIP with a high-titre antiserum antagonized inhibitory neuromuscular transmission in the LOS. These findings provide evidence of a role for VIP as an inhibitory neurotransmitter.