CART (62-76) (rat, human)

Effects of ghrelin and other neuropeptides (CART, MCH, orexin A and B, and GLP-1) on the release of insulin from isolated rat islets.[Pubmed:12883265]

Pancreas. 2003 Aug;27(2):161-6.

BACKGROUND AND AIMS: Ghrelin, a neuropeptide containing 28 amino acids, shows a reciprocal diurnal plasma fluctuation to that of plasma insulin. The aim of this study is to clarify the dose and glucose-dependency of ghrelin on the insulin secretion and to compare its effect with that of other neuropeptides-GLP-1, CART (55-102), CART (55-76), CART (62-76), MCH, orexin A, and B. MATERIALS AND METHODS: Rat islets were incubated with 1 pmol/l-1 micromol/l of ghrelin, CART fragments, MCH, orexin A or B, or GLP-1 (n = 16-32) in the presence of 16.7 mmol/l glucose. Ghrelin (10 nmol/l) was added to islets at glucose concentrations of 3.3, 6.6, 16.7 and 25 mmol/l, respectively (n = 28-32). Also, INS-1E cells were incubated with ghrelin (1 nmol/l) in the presence of glucose (3.3, 6.6, 16.7, and 25 mmol/l). In addition, we measured the mRNA expression of the ghrelin receptor using RT-PCR. RESULTS: Ghrelin inhibited insulin secretion from islets and INS-1E cells in a dose- and glucose-dependent manner. Neither 10 pmol/l-1 micromol/l of CART fragments, MCH, orexin A, nor orexin B changed the insulin secretion at 16.7 mmol/l glucose, while GLP-1, as expected, stimulated the insulin release from rat islets. Interestingly, ghrelin receptors were expressed both in islets, INS-1E, MIN 6 and alpha cell Tca-9 lines. CONCLUSIONS: Ghrelin inhibits the insulin secretion in vitro in a dose- and glucose-dependent manner. Beta cells contain ghrelin receptors. CART fragments did not affect the insulin secretion. Ghrelin may play a physiological role for the regulation of insulin secretion.

Cocaine and amphetamine-regulated transcript peptide (CART(62-76))-induced changes in regional monoamine levels in ratbrain.[Pubmed:12030814]

Neuropeptides. 2001 Oct-Dec;35(5-6):292-6.

Cocaine- and amphetamine-regulated transcript (CART) is a novel neuropeptide with neurotransmitter-like effects. In the present study we examined the influence of CART peptide fragment, CART(62-76), on the levels of catecholamines (dopamine and norepinephrine), serotonin and their metabolites in five regions of the rat brain. CART(62-76) was administered at 0.5 or 5.0 microg dose intracerebroventricularly. A high-pressure liquid chromatograph coupled to electrochemical array detector was used to analyse the tissue homogenates. In the frontal cortex, CART(62-76) increased the levels of 5-hydroxyindoleacetic acid (5-HIAA), a metabolite of serotonin (5-HT). In the striatum, CART(62-76) decreased the levels of noradrenaline and 5-HT. In the hypothalamus, CART(62-76) increased the levels of 5-HIAA. CART(62-76) had no significant effect in the hippocampus and cerebellum. Our data suggest that CART(62-76) peptide has no major effect on dopaminergic pathways, but it modulates the activity of striatal noradrenergic and corticostriatal and hypothalamic serotoninergic system in the rat brain. These regionally selective neurochemical changes may explain the effects of CART peptides on appetitive, emotional and locomotor behaviour.

Effects of CART peptides on food consumption, feeding and associated behaviors in the goldfish, Carassius auratus: actions on neuropeptide Y- and orexin A-induced feeding.[Pubmed:11134597]

Brain Res. 2000 Dec 22;887(1):125-33.

CART (cocaine- and amphetamine-regulated transcript) peptides are novel brain neuropeptides that have been shown to have a role in the control of feeding behavior in mammals. The effects of intracereboventricular (i.c.v.) administration of two CART fragments, CART (62-76) and CART (55-102) on feeding and behavioral activity of goldfish (Carassius auratus) were examined. Both CART peptide fragments inhibited food intake in goldfish. Co-injection of CART peptide and neuropeptide Y (NPY) reduced the increase in feeding caused by injection of NPY alone. CART (55-102) was more potent than CART (62-76). Co-treatment with CART (55-102) and orexin A inhibited the feeding response induced by orexin A alone. Feeding behavior was stimulated relative to saline controls following injection of CART (62-76) alone and co-injection of NPY and CART (62-76), but was not affected by treatment with CART (55-102) alone, NPY and CART (55-102) or orexin A and CART (55-102). Total behavioral activity was increased with NPY, orexin A, and both CART fragments alone as compared to saline controls, as well as in fish co-treated with NPY and CART (62-76) or NPY and CART (55-102) as compared to saline controls and NPY-treated fish. Tremors were seen in fish treated with CART (55-102) alone, and in fish co-treated with NPY and CART (55-102) and orexin A and CART (55-102). Co-treatment of the fish with NPY but not with orexin A significantly lowered the frequency of fish showing tremors as compared to fish treated with CART alone. These results indicate that CART peptides are involved in the regulatory pathways of feeding and behavioral activity in goldfish.