We have reported previously that the transmembrane domains of the cholecystokinin-B/gastrin receptor (CCK-BR) comprise a putative ligand binding pocket. In the present study, we examined whether amino acid substitutions within the CCK-BR pocket altered the affinities and/or functional activities of L-365,260 (the prototypical nonpeptide CCK-BR antagonist) and two structural derivatives, YM022 (...

Cholecystokinin (CCK) influences gastrointestinal motility, by acting on central and peripheral receptors. The aim of the present study was to determine whether CCK has any effect on isolated duodenum longitudinal muscle activity and to characterize the mechanisms involved. Isolated segments of the rat proximal duodenum were mounted for the recording of isometric contractions of longitudinal mu...

Cholecystokinin octapeptide (CCK-8), a gut-brain peptide, regulates a variety of physiological behavioral processes. Previously, we reported that exogenous CCK-8 attenuated morphine-induced conditioned place preference, but the possible effects of CCK-8 on aversively motivated drug seeking remained unclear. To investigate the effects of endogenous and exogenous CCK on negative components of mor...

The immune system in vertebrates senses exogenous and endogenous danger signals by way of complex cellular and humoral processes, and responds with an inflammatory reaction to combat putative attacks. A strong protective immunity is imperative to prevent invasion of pathogens; however, equivalent responses to commensal flora and dietary components in the intestine have to be avoided. The autono...

Cholecystokinin (CCK) may mediate human anxiety and animal data suggest that cholecystokinin antagonists could provide an important advance in the treatment of anxiety disorders. The study of CCK receptor systems in psychiatric patients has, however, been severely limited by the lack of available probes. We utilized intravenous infusions of pentagastrin, a selective CCK-B receptor agonist, and ...

The subfornical organ (SFO) is an important sensory circumventricular organ implicated in the regulation of fluid homeostasis and energy balance. We investigated whether the SFO is activated by the hormone cholecystokinin (CCK). CCK₁ and CCK₂ receptors were identified in the SFO by RT-PCR. Dissociated SFO neurons that responded to CCK (40/77), were mostly depolarized (9.2 ± 0.9 mV, 30/77), but ...

We have previously reported that CCK-A receptor agonists and CCK-B receptor antagonists both enhance memory in an olfactory recognition test. Here, we report that the memory-enhancing effect of the CCK-B receptor antagonist L-365,260 (1 mg/kg i.p.), but not that of the CCK-A receptor agonist caerulein (0.03 mg/kg i.p.), was dramatically decreased following a bilateral transection of the perfora...

Previous studies suggested that peripheral immune mediators may involve intermediates acting on the vagus nerve, such as CCK or serotonin (5-HT). We have therefore investigated a possible role for vagal CCK-A and 5-HT(3) receptors in the febrile response after intraperitoneal human recombinant interleukin-1beta (IL-1beta) or lipopolysaccharide (LPS). Unanesthetized, adult male rats instrumented...

Cholecystokinin (CCK) is a peptide originally discovered in the gastrointestinal tract but is also found in high density in the mammalian brain. The C‐terminal sulfated octapeptide fragment of CCK8 constitutes one of the major neuropeptides in the brain. CCK8, interacting with nanomolar affinities with two different receptors designated CCK1 and CCK2, has been shown to be involved in numerous p...