PHARMACOLOGICAL DISSOCIATION OF RESPONSES TO CCK AND GASTRIC LOADS INRAT MECHANOSENSITIVE VAGAL AFFERENTS

To identify the transduction mechanisms underlying gastric vagal affer ent responses to gastric loads and cholecystokinin (CCK), we investiga ted the ability of specific CCK antagonists, acute pylorectomy, and ch olinergic blockade to effect these vagal afferent responses. The CCK-B antagonist L-365,260 (10 pmol-1 nmol) failed to block the gastric vag al afferent response to gastric loads or 100 pmol CCK, while the CCK-A antagonist devazepide (100 pmol-100 nmol) competitively and dose depe ndently attenuated the response to CCK but not to gastric loads. Appli cation of 100 nmol of the low-affinity CCK receptor antagonist CCK-JMV -180 also completely blocked the gastric vagal afferent response to 10 0 pmol CCK. Acute pylorectomy failed to block the gastric vagal affere nt response to 100 pmol CCK or 2-ml gastric loads. Atropine sulfate ad ministration (15 mg/rat) failed to block the gastric vagal afferent re sponse to 100 pmol CCK or 2-ml gastric loads. These data suggest that 1) the vagal afferent response to CCK is mediated through CCK's intera ctions with vagal, rather than pyloric, CCK-A receptors, and 2) the va gal afferent responses to CCK and to gastric loads are mediated by dis sociable, possibly independent, transduction mechanisms.