Abstract

The mechanism of action of bombesin in the longitudinal muscle with myenteric plexus (LM-MP) preparation from guinea pig ileum was examined. Bombesin (3 x 10(-10) to 3 X 10(-7) M) induced contraction in a concentration-dependent manner. The contractions induced by bombesin at concentrations of 10(-9) M and less were tetrodotoxin- and scopolamine-sensitive, and those induced at concentrations of 10(-8) M and greater were tetrodotoxin-sensitive, and partially scopolamine-sensitive. In association with the mechanical response to bombesin, the peptide induced Ca(++)-dependent and tetrodotoxin-sensitive release of acetylcholine from the LM-MP preparation. Bicuculine inhibited partly both the cholinergic contraction and the release of acetylcholine induced by bombesin, suggesting the involvement of a gamma-aminobutyric acid (GABA)-ergic mechanism. Bombesin also induced Ca(++)-dependent and tetrodotoxin-sensitive release of endogenous and [3H]GABA from the LM-MP preparation. These results indicate that bombesin induces contraction mainly mediated mediated by cholinergic and partially mediated by noncholinergic excitatory neurons. GABAergic neurons may be involved in a part of the response to bombesin mediated by the cholinergic neuron.