Suppression of inhibitory neural input to colonic circular muscle by opioid peptides

The aim of this study was to identify the neurotransmitter responsible for the dominant inhibitory neural input that normally masks myogenic phasic activity in the intestine. Opioid agonists, including opioid derivatives of proenkephalin and prodynorphin, caused direct tonic and indirect phasic contractions of strips from the circular muscle layer of rat colon. Both contractile responses appeared to be mediated by preferential interaction with delta opioid receptors. Elimination of most, if not all, neural input with tetrodotoxin (TTX) induced concentration-dependent phasic contractions. Neutralization of background vasoactive intestinal peptide (VIP) with VIP antiserum induced phasic contractions in previously quiescent muscle strips. The effect of VIP antiserum was concentration-dependent in the range of 1:960 to 1:60. A threshold concentration of VIP antiserum (1:960) increased the sensitivity of the phasic responses to [Met]enkephalin (100-fold) and TTX (20-fold) whereas exogenous VIP had the opposite effect. [Met]enkephalin and TTX inhibited basal VIP release by 43 +/- 8% (P less than .001) and 65 +/- 13% (P less than .01), respectively. It was concluded that VIP was the neurotransmitter responsible for the dominant inhibitory neural input to intestinal circular muscle and that opioid peptides induce phasic contractions by suppressing VIP release.