Vasoactive intestinal polypeptide: a transmitter in submucous neurons mediating secretion in guinea pig distal colon.

The aim of the study was to investigate the role of vasoactive intestinal polypeptide (VIP) as a transmitter in regulation of epithelial function. Submucosa/mucosa segments from guinea pig distal colon were mounted in flux chambers and increases in short-circuit current were used as an index of secretion. Serosal addition of VIP, peptide histidine isoleucine, helodermin and pituitary adenylate cyclase-activating peptide caused an increase in short-circuit current. Tissues were less responsive to peptide histidine isoleucine, helodermin and pituitary adenylate cyclase-activating peptide than to VIP. In tissues without neurogenic tone, VIP(10-28), but not tetrodotoxin, reduced the response to exogenous VIP. The secretory response to VIP was attenuated by tetrodotoxin and atropine only in tissues with ongoing neural activity influencing basal rates of transport. In the presence of muscarinic blockade, neural stimulation evoked an increase in short-circuit current which was attenuated by VIP(10-28). High extracellular potassium concentrations or carbachol evoked release of endogenous VIP. VIP and VIP (10-28) displaced the binding of [125I]VIP to epithelial receptors. These results provide evidence that VIP is a neurotransmitter within the submucous plexus involved in regulation of epithelial transport in the guinea pig colon.