[Cholecystokinins and their receptors. Functional aspects].
The term cholecystokinin (CCK) refers to a family of related peptides whose members play hormonal roles in the gastro-intestinal tract. The sulfated octapeptide CCK-8 [Asp-Tyr(SO3H)-Met-Gly-Trp-Met-Asp-Phe-NH2] is also abundant throughout the central nervous system where it satisfies the criteria for a neurotransmitter. CCK interacts with at least two types of receptor called CCK-A and CCK-B receptors. These binding sites can be distinguished on the basis of their affinities for different molecular forms of CCK. Moreover, selective nonpeptide antagonists have been developed for CCK-A and CCK-B receptors. CCK-A receptors occur predominantly at the peripheral level where they are responsible for the digestive effects of CCK: intestinal and biliary smooth muscle contraction, pancreatic enzyme secretion, trophic effects on gastric and intestinal mucosa and regulation of feeding. Some brain CCK-receptors belong to the A-type, but the majority of them are CCK-B receptors. High densities of brain CCK-B receptors are present in cortical and limbic areas such as the amygdala and the hippocampus. At the peripheral level, CCK-B receptor antagonists are active on gastrin receptors, and these two receptors are similar if not identical. Experimental evidence suggests involvement of brain CCK processes in 4 domains: modulation of dopaminergic function, control of pain sensation, anxiety and memory formation. Thus, CCK-B antagonists may be useful to treat certain neuropathological conditions associated with CCK dysfunction.
Böhme
G A
GA
Rhône-Poulenc Rorer, Centre de Recherches de Vitry-Alfortville, Vitry-sur-Seine.
Blanchard
J C
JC
D000818:Animals; D002490:Central Nervous System / Q000187:drug effects; D002766:Cholecystokinin / Q000494:pharmacology*; D004064:Digestive System / Q000187:drug effects; D006801:Humans; D066298:In Vitro Techniques; D011949:Receptors, Cholecystokinin / Q000037:antagonists & inhibitors / Q000502:physiology*
D011949:Receptors, Cholecystokinin; D002766:Cholecystokinin
Les cholécystokinines et leurs récepteurs. Aspects fonctionnels.