Effects of bombesin on mucosal ion transport in the mouse isolated jejunum

The effects of bombesin (BBS) on ion transport in the mouse isolated jejunum were studied in full thickness (intact) or serosal stripped (mucosal) sheets of jejunum mounted in Ussing chambers. Although serosal BBS (0.1-30 nM) induced a concentration-related increase in transmural potential difference (PD) and short-circuit current (I(sc)) without altering conductance in both preparations, the peptide was more potent and efficacious in mucosal than in intact tissues. In all preparations, pretreatment with BBS abolished the effects of a subsequent administration of BBS showing the rapid development of desensitization. In intact tissues, serosal pretreatment with either chlorisondamine (3 μM) or tetrodotoxin (0.1 μM) decreased, but did not abolish BBS action. Meanwhile, atropine pretreatment (3 μM) did not affect the BBS response. In these tissues, previous blockade of NaCl cotransport by furosemide (300 μM) decreased BBS (30 nM) stimulation of PD or I(sc). In mucosal preparations, tetrodotoxin pretreatment (0.1 μM) similarly reduced but did not eliminate BBS (3 nM) stimulation of PD or I(sc), whereas atropine pretreatment (1 μM) again had no effect on BBS action. In contrast in these mucosal tissues, furosemide pretreatment (300 μM) did not modify the BBS response. Furthermore, carbachol pretreatment (10 μM) prevented completely the tetrodotoxin-resistant action of BBS. These findings in vitro suggest that the increase of PD and I(sc) following BBS administration in isolated mouse jejunum is associated with three different levels of action of this peptide: BBS may act on noncholinergic nerves, at pre- and post-ganglionic levels, as well as directly on the enterocyte. Although the action on the enteric nervous system may mainly stimulate Cl^- secretion, other ions could be involved in the direct action of BBS on the enterocyte. This last action involves intracellular mechanisms that may be shared, in part, with those activated by carbachol.