Response of the gastric vagal afferent activity to cholecystokinin in rats lacking type A cholecystokinin receptors.

A systemic administration of cholecystokinin (CCK) increases gastric vagal afferent activity via type A CCK receptors (CCKAR). In the present study, the response of gastric vagal afferent activity to an intravenous administration of CCK was investigated in Otsuka Long-Evans Tokushima Fatty (OLETF) rats, which lack CCKAR, and compared with its control strain, Long-Evans Tokushima Otsuka (LETO) rats. The intravenous administration of 300 pmol kg(-1) and 3 nmol kg(-1) of CCK elicited dose-dependent increases in the gastric vagal afferent activity in LETO rats. The responses were not influenced by the pretreatment with L-365,260, a type B CCK receptor (CCKBR) antagonist, while they were significantly diminished by pretreatment with MK-329, a CCKAR antagonist. After pretreatment with MK-329, 3 nmol kg(-1) (but not 300 pmol kg(-1)) of CCK still elicited a small but significant increase in the activity. In the OLETF rats, both 300 pmol kg(-1) and 3 nmol kg(-1) of CCK produced small increases in the vagal afferent activity, and the responses were not influenced by pretreatment with either L-365,260 or MK-329. In addition, the systemic administration of CCK did not change gastric motility in the OLETF rats, indicating that the response of the vagal afferent activity in OLETF rats was independent of the gastric motility change. These results demonstrate that neither CCKAR nor CCKBR contributes to the response of the afferent activity of the gastric vagal nerve to a systemic administration of CCK in OLETF rats, suggesting an involvement of novel (non-A, non-B) CCK receptors.