Bombesin acts in the brain to decrease gastric vagal efferent discharge in rats.

The central nervous system action of bombesin to influence basal gastric vagal efferent discharge (GVED) was investigated in urethane-anesthetized rats. Bombesin (62, 620, and 6200 pmol) injected intracisternally (IC) decreased GVED to 78 +/- 10%, 50 +/- 4%, and 43 +/- 3% of preinjection levels, respectively. Bombesin (620 pmol) injected IV also reduced GVED to 36 +/- 6%. Pretreatment with bombesin monoclonal antibody 2A11 completely prevented the decrease in GVED induced by bombesin (620 pmol) given IV but not IC. These data indicate that both IC and IV injections of bombesin decrease basal GVED, and that the inhibitory effect of IC injection represents a central nervous system-mediated action.

Peripheral bombesin decreases gastric vagal efferent activity in part through vagal pathways in rats.

The influence of intravenous (iv) bombesin on multiunit activities recorded from the ventral gastric branch of the vagus was investigated in urethan-anesthetized rats. Consecutive injections of bombesin (0.062, 0.62, 6.2, 62, and 620 pmol iv) decreased dose dependently gastric vagal efferent discharges to 79.8 +/- 4.9, 68.3 +/- 10.2, 47.0 +/- 6.7, 41.6 +/- 4.7, and 36.5 +/- 8.9%, respectively, from preinjection levels. Saline injection had no effect. Bombesin (62 pmol iv) reduced cervical vagal efferent discharges to 25 +/- 6% before and 67 +/- 5% after bilateral cervical vagotomy distal to the recording site. Bombesin (62 and 620 pmol iv) increased gastric vagal afferent discharges by 45 and 93%, respectively. These data show that systemic injection of bombesin potently decreases gastric and cervical vagal efferent activity in part through vagal-dependent mechanisms that may involve the increase in gastric vagal afferent activity.

Peripheral bombesin induces gastric vagal afferent activation in rats.

Bombesin's influence on gastric vagal afferent discharge (GVAD) was studied in urethan-anesthetized rats. Vehicle and peptides were injected intravenously at 30-min intervals. Cholecystokinin (CCK; 300 pmol) and bombesin (300 pmol) increased ongoing multiunit GVAD by 153 +/- 59 and 162 +/- 37%, respectively; similar increases were induced by a second injection of bombesin and CCK. The bombesin antagonist, ICI-216140, prevented bombesin-induced increase in GVAD, whereas the CCK response was not influenced. The CCK-A receptor antagonist devazepide reduced the activation of GVAD induced by bombesin from 107 +/- 11 to 63 +/- 6%, while abolishing the CCK response. Devazepide given alone or in combination with ICI-216140 did not modify gastric distension (3 ml)-induced increase in GVAD. Of 22 single units that were activated by gastric load (4 ml), 17 and 20 units responded also to bombesin (620 pmol) and CCK (870 pmol), respectively. Of the nine units that did not respond to gastric load, eight had an increase in GVAD induced by both bombesin and CCK. There was no specific binding of 125I-labeled [Tyr4]bombesin on cervical vagus, either intact or 24 h after ligation. These data suggest that intravenous bombesin-induced stimulation of GVAD is indirect and initially mediated through specific receptor activation influencing gastric smooth muscle and the release of CCK.