Role of cholecystokinin in feeding and lactation.
The aim of this investigation was to study the release of cholecystokinin (CCK) in connection with feeding and lactation and to investigate the involvement of CCK in the regulation of food intake. For this purpose a method based on high performance liquid chromatography and subsequent radioimmunoassay (RIA) for the determination of CCK in plasma was developed. CCK was also determined in the cerebrospinal fluid (CSF) by RIA and is referred to as CCK-like immunoreactivity (CCK-LI). Different molecular forms of CCK in dog and rat plasma have been determined. These were found to differ from those in the CSF, suggesting that the CCK measured in plasma and CSF are derived from different sources, i.e. the gut and brain. CCK was released into plasma in response to feeding in dogs and rats and in response to suckling in lactating animals. The release of CCK is under vagal control. Thus, electrical vagal stimulation of anaesthetized rats increased plasma levels of CCK, and abdominal vagotomy abolished the suckling-induced release of CCK. Lesions of the lateral midbrain, which disrupt the oxytocin-mediated milk-ejection reflex, were also found to block the increase in plasma CCK in response to suckling. Intraperitoneal (i.p.) injection of CCK octapeptide (CCK-8) decreased food intake in food deprived male rats in doses which resulted in plasma concentrations within the physiological range. Intracerebral, but not i.p., injection of a low dose of a CCK antagonist, reversed the effect of peripheral CCK-8 on food intake as did i.p. injection of peripheral CCK A receptor antagonists. Thus, the mechanism by which i.p. CCK-8 inhibits food intake may involve both peripheral and central CCK receptor mechanisms. The concentration of CCK-LI in the CSF decreased after food deprivation and increased after feeding or i.p. CCK-8. Intraperitoneal injection of peripheral CCK antagonists prevented the increase in CCK-LI in the CSF and the inhibitory effect of i.p. CCK-8 on food intake. These data indicate that peripheral CCK receptor mechanisms induce a release of CCK in the brain. During the hyperphagia of lactation, plasma but not CSF levels of CCK were increased in the rat. Food deprivation markedly decreased the concentration of CCK in plasma and CSF; and the levels were restored in CSF, but not in plasma, after 1 h of feeding. Removal of the litter decreased food intake and increased the concentration of CCK in the CSF, but not in plasma. Lactating rats were less sensitive to the inhibitory effect of i.p.(ABSTRACT TRUNCATED AT 400 WORDS)
Lindén
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Department of Pharmacology, Karolinska Institutet, Stockholm, Sweden.
D000818:Animals; D002766:Cholecystokinin / Q000097:blood* / Q000134:cerebrospinal fluid; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D004285:Dogs; D004435:Eating / Q000502:physiology; D005260:Female; D007774:Lactation / Q000097:blood* / Q000134:cerebrospinal fluid; D008893:Milk Ejection / Q000502:physiology; D011247:Pregnancy; D011270:Pregnancy, Animal / Q000097:blood* / Q000134:cerebrospinal fluid; D011863:Radioimmunoassay / Q000379:methods; D051381:Rats; D012844:Sincalide / Q000008:administration & dosage; D014630:Vagus Nerve / Q000502:physiology
D002766:Cholecystokinin; D012844:Sincalide