The Physiology of Cholecystokinin in Brain and Gut

Abstract

PHYSIOLOGY OF CHOLECYSTOKININ IN BRAIN AND GUT GJDockray used in biological studies before it became clear that this fragment existed naturally in its own right The identification of CCK8 was made first in extracts of brain of the rat, pig, dog and man, and followed reports of gastrin-like immunoreactivity in brain (Vanderhaeghen et al. 1975; Dockray, 1976; Muller et al. 1977; Rehfeld, 1978). The latter material was reported to occur in high concentrations in cerebral cortex and to have the gel-filtration properties of a molecule smaller than the main forms of gastrin. It is now clear that this material is attributable to CCK8, which cross-reacts with some C-terminal specific gastrin antisera because of the common C-terminal pentapeptide of the two substances (fig. 1). Soon after the identification of CCK8 in brain this material was isolated and shown to possess the full chemical and biological properties of the synthetic peptide (Dockray et al. 1978). A closely related variant of CCK8 that is also biologically active, but on anion-exchange chromatography appears to be slightly less acidic, was isolated as well, but has not yet been fully characterized. All the characterized forms of CCK have a sulphated tyrosine residue at position seven counting from the C terminus. Radioimmunoassay studies using antisera that react equally with sulphated and unsulphated CCK 8 indicate that the desulphated form does not occur naturally in detectable amounts (Dockray, 1980). In contrast, the structurally related hormone gastrin, which also has a tyrosine in the C-terminal region (although in this case at position six from the C terminus), occurs in antral mucosa in about equal proportions of sulphated and unsulphated forms (see Gregory, 1982). The sulphate group is essential for the main gastrointestinal actions of CCK8, but its significance for the neuronal actions of this peptide are less obvious (see section 3).

Evaluation of a new and potent cholecystokinin antagonist on motor responses of the guinea‐pig intestine

“…In this context, it is worth noting that the CCK receptors in the gall bladder and the pancreatic acini seem to be located on nonneuronal cells (Yau et al, 1973;Williams, 1982), whereas those in the guinea-pig ileum are located on enteric neurones (see Introduction). It would appear, therefore, that peripheral CCK receptors share a similar sensitivity to CR 1409 which is independent of their location, an assumption that has also been raised by Dockray (1982) with regard to dibutyryl cyclic guanosine monophosphate. The specificity of CR 1409 as a CCK antagonist was proved by the finding that contractions of the longitudinal and circular muscles of the guinea-pig ileum, induced by a variety of non-CCK agonists, were not affected.…”

Renal effects of gastrin C‐terminal tetrapeptide (as pentagastrin) and cholecystokinin octapeptide in conscious rabbit and man

“…sium excretion; an overall effect resembling the potassium-sparing diuretics, amiloride and triamterene (Reineck & Stein, 1981). The rise in plasma glucose concentration observed during CCK8 infusion in the rabbit may, or may not, be direct (Unger et al, 1967;Dockray, 1981), but could be a factor in CCK8-induced appetite suppression (Dockray, 1982).…”

5-HT3receptors participate in CCK-induced suppression of food intake by delaying gastric emptying

“…One such response is the mediation of nutrient-induced inhibition of gastric emptying (49). Similar to 5-HT, one mechanism by which CCK suppresses food intake is through its ability to inhibit gastric emptying (3,12,19,36,40,43,55).Previous studies have shown an interaction between the serotonergic and cholecystokinergic systems in the control of food intake (7,8,47). Although original exploration of this interaction focused on central serotonergic activity, recent reports (11), including those from our own laboratory (22), have shown that systemic administration of a selective 5-HT 3 receptor antagonist attenuates CCK-induced satiation.…”

“…One such response is the mediation of nutrient-induced inhibition of gastric emptying (49). Similar to 5-HT, one mechanism by which CCK suppresses food intake is through its ability to inhibit gastric emptying (3,12,19,36,40,43,55).…”