Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P01178 (oxytocin)
 15,767 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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)
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PMID:Role of cholecystokinin in feeding and lactation. 260 47

Cholecystokinin-octapeptide (CCK8) administered intraperitoneally (i.p.) in rats induces a rapid elevation in serum oxytocin (OT). The receptor subtype mediating this action of CCK was investigated with selective CCK-A and CCK-B receptor agonists and antagonists. CCK8 and A-71623, a potent CCK-A selective agonist, were similar in efficacy and potency for stimulating OT secretion. Both compounds at 10 nmol/kg elicited approximately one-half the response of 100 nmol/kg, which elevated serum OT to approx. 20 to 30-fold above basal level. The potent CCK-B selective agonist, A-63387, at doses up to 100 nmol/kg did not increase serum OT. MK-329, a CCK-A receptor selective antagonist, at a dose of 20 nmol/kg fully inhibited the action of 20 nmol/kg CCK8, while 100 nmol/kg of (R)L-365,260, a CCK-B selective antagonist, had no effect on the CCK8 response. These results, together with previous lesion studies, suggest that vagal CCK-A receptors in the periphery mediate the activation of the oxytocinergic pathway in vivo.
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PMID:Peripheral cholecystokinin type A receptors mediate oxytocin secretion in vivo. 842 7

Cholecystokinin (CCK) has been suggested to mediate satiety in a number of non-primate species via its peripheral actions as well as a possible central mechanism involving magnocellular and parvocellular oxytocin release. Quantitative in vitro autoradiography employing [125I]-Bolton-Hunter labelled CCK-8S ([125I]-CCK-8S) was used to examine the distribution and density of CCK receptors in sections of brain from normal rats and rats deprived of food, water or both food and water for 4 days. In food-deprived rats, specific [125I]-CCK-8S binding was reduced by 64 +/- 5% in the hypothalamic supraoptic nucleus (SON) and by 44 +/- 13% in the paraventricular nucleus of the hypothalamus (PVN). In contrast, water deprivation increased binding of [125I]-CCK-8S by 128 +/- 15% in the SON and by 196% +/- 24% in the PVN, while combined food and water deprivation produced smaller increases in both nuclei (30 +/- 5% and 98 +/- 26% in SON and PVN respectively). Changes in receptor density in the PVN appeared to be most prominent in the magnocellular (especially oxytocin-rich) subdivisions. None of the treatments employed produced changes in [125I]-CCK-8S binding in the ventromedial hypothalamic nucleus or the reticular thalamic nucleus. Both CCK-A and CCK-B receptor subtypes were visualized in the nucleus of the solitary tract and the area postrema of normal rats, but levels of binding to both of these subtypes were unaffected by the experimental treatments. These selective alterations demonstrate the plasticity of CCK receptors in the SON and PBN, and are probably associated with changes in the level of neurochemical activity of magnocellular oxytocinergic neurones in these areas. These results, together with reports of changes in the level of CCK synthesis in cells of the SON and PVN after hyperosmotic stimuli, suggest that CCK may act in an autocrine fashion on these neurones and that both CCK receptors and peptide levels are altered in the same direction following cellular activation or inhibition.
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PMID:Regulation of cholecystokinin receptors in the hypothalamus of the rat: reciprocal changes in magnocellular nuclei induced by food deprivation and dehydration. 868 Apr 44

This issue of Peptides was inspired by a gathering of CCK researchers at the first Neuronal Cholecsytokinin Gordon Conference. The papers in this issue reflect the diversity of CCK research and demonstrate how the field has matured. Reviews describe the regulation of CCK gene expression and CCK release, the nature of the hormone binding site of the CCK A receptor, interaction of CCK, dopamine and GABA, the role of CCK in thermoregulation, sexual behavior and satiety in rodents and humans. The research articles document features of cardiovascular regulation, reduced cocaine sensitization and decreased satiety in rats that lack the CCK A receptor. Pro CCK processing in neuroblastoma cells and the elevation of CCK levels in CSF in a model of chronic pain are detailed in other articles. Three articles using different behavioral paradigms in rat and sheep examine CCK in learning and memory. Two articles that examine CCK in different behaviors that have a dopaminergic component are included. Other articles describe the interaction between a 5HT(3) antagonist and CCK-induced satiety and c-fos activation and document secretion of oxytocin and vasopressin in female patients and controls in response to CCK 4 administration. There is good reason to believe that the future is bright for research on CCK. With the organization of national and international meetings, CCK researchers have a forum for communication. Opportunities for cooperation and collaboration have never been better. The easy integration of academic basic and clinical science with industrial science bodes very well for the advancement of our understanding of the multiple roles that CCK plays in the brain and for the future development of CCK-based therapies.
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PMID:An introduction to neuronal cholecystokinin. 1145 11

These experiments were performed to study the effect of oxytocin (OT) and it's specific receptor on gallbladder motility in rabbits. The fasted New Zealand white rabbits (2.0-2.5 kg) were anaesthetized by urethane (1 g/kg). The gallbladder pressure was recorded continuously to monitor the gallbladder motility. Systemic OT (0.01, 0.02, 0.04 mg/kg, iv) did not affect the gallbladder pressure, but dose-dependently increased the frequency of phasic contraction. Five min after OT administration (0.04 mg/kg, iv), the strength of phasic contraction increased to 0.23 +/- 0.08 mmHg/min (P < 0.01, n = 6). The gallbladder motility returned to normal 15 min later after OT treatment. Intravenous injection of atosiban (0.04 mg/kg, iv), an OT receptor antagonist, decreased the strength of gallbladder phasic contraction but did not affect gallbladder pressure. Pretreatment of atosiban (0.04 mg/kg, iv) completely abolished the systemic OT effect on gallbladder. Vasopressin (VP) (0.1 - 0.5 IU/kg, iv) dose-dependently decrease the gallbladder pressure but did not affect the phasic contraction. MK-329 (0.4 mg/kg, iv), the CCK-A receptor antagonist, L-365, 260 (0.4 mg/kg, iv), the CCK-B receptor antagonist and atropine (0.2 mg/kg, iv), the M receptor antagonist, did not affect the OT effect on gallbladder motility. We suggest that endogenous OT regulates gallbladder phasic contraction through specific OT receptor. This effect is independent of the peripheral CCK and M receptors.
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PMID:Endogenous oxytocin excites phasic contraction of gallbladder in rabbits through oxytocin receptor. 1467 77

Peripheral administration of cholecystokinin (CCK)-8 selectively activates oxytocin (OXT)-secreting neurons in the supraoptic (SON) and the paraventricular nuclei (PVN) with the elevation of plasma OXT level in rats. We examined the effects of intravenous (iv) administration of CCK-8 on the neuronal activity of hypothalamic OXT-secreting neurons and plasma OXT level in Otsuka Long-Evans Tokushima Fatty (OLETF) rats that have a congenital defect in the expression of the CCK-A receptor gene. In situ hybridization histochemistry (ISH) for c-fos mRNA revealed that the expression of the c-fos gene was not induced in the SON, the PVN, the nucleus of the tractus solitarius (NTS) and the area postrema (AP) 30 min after iv administration of CCK-8 (20 and 40 microg/kg) in OLETF rats. In Long-Evans Tokushima Otsuka (LETO) rats (controls), c-fos mRNA was detected abundantly in those nuclei 30 min after iv administration of CCK-8 (20 microg/kg). Immunohistochemistry for c-fos protein (Fos) showed that the distributions of Fos-like immunoreactivity (LI) were identical to the results obtained from ISH. Dual immunostaining for OXT and Fos revealed that Fos-LI was mainly observed in OXT-secreting neurons in the SON and the PVN of LETO rats 90 min after iv administration of CCK-8 (20 microg/kg). Radioimmunoassay for OXT and arginine vasopressin (AVP) showed that iv administration of CCK-8 did not cause significant change in the plasma OXT and AVP levels in OLETF rats, while iv administration of CCK-8 caused a significant elevation of plasma OXT level without changing the plasma AVP level in LETO rats. These results suggest that peripheral administration of CCK-8 may selectively activate the hypothalamic OXT-secreting neurons and brainstem neurons through CCK-A receptor in rats.
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PMID:Effects of cholecystokinin (CCK)-8 on hypothalamic oxytocin-secreting neurons in rats lacking CCK-A receptor. 1597 47

Neurokinin 3 receptor (NK3R) signaling has an integral role in the stimulated oxytocin (OT) and vasopressin (VP) release in response to hyperosmolarity and hypotension. Peripheral injections of cholecystokinin (CCK) receptor agonists for the CCK-A (sulfated CCK-8) and CCK-B (nonsulfated CCK-8) receptors elicit an OT release in rat. It is unknown whether NK3R contributes to this endocrine response. Freely behaving male rats were administered an intraventricular pretreatment of 250 or 500 pmol of SB-222200, a specific NK3R antagonist, or 0.15 M NaCl before an intraperitoneal or intravenous injection of CCK-8 (nonsulfated or sulfated) or 0.15 M NaCl. Blood samples were taken before intraventricular treatment and 15 min after intraperitoneal or intravenous injection, and plasma samples were assayed for OT and VP concentration. Intraperitoneal injection of both nonsulfated and sulfated CCK-8 significantly increased plasma OT levels and had no effect on plasma VP levels. Intravenous injection of sulfated CCK-8 stimulated an increase in plasma OT levels and did not alter plasma VP levels. However, intravenous injection of nonsulfated CCK-8 stimulated a significant increase in plasma levels of both OT and VP. No other studies have demonstrated CCK-8-stimulated release of VP in rat. NK3R antagonist did not alter baseline levels of either hormone. However, pretreatment of NK3R antagonist significantly blocked the CCK-stimulated release of OT in all CCK treatment groups and blocked VP release in response to intravenous injection of nonsulfated CCK-8. Therefore, central NK3R signaling is required for OT and VP release in response to CCK administration.
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PMID:Tachykinin neurokinin 3 receptor signaling in cholecystokinin-elicited release of oxytocin and vasopressin. 1838 72