Effect of opioid antagonism on β-endorphin processing and proopiomelanocortin-peptide release in the hypothalamus

Jaffe, Sharon B.; Sobieszczyk, S; Wardlaw, Sharon L.

doi:10.1016/0006-8993(94)91900-3

Cited by 27 publications

(26 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the fractionation of ␤-endorphin and ACTH, the gradient was 30 -35% B for the initial 5 min, 35-45% B for the next 45 min, and then to 50% B over the next 5 min (27). For the fractionation of ␣-MSH, the gradient was 15-45% B for the first 30 min and then to 65% B over the next 10 min.…”

Section: Methodsmentioning

confidence: 99%

Impaired Prohormone Convertases in Cpe fat/Cpe fat Mice

Berman¹,

Mzhavia²,

Polonskaia³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

. (1995) Nat. Genet. 10, 135-142). Examination of the level of neuropeptides in these mice showed a decrease in mature bioactive peptides as a result of a decrease in both carboxypeptidase and prohormone convertase activities. A defect in CPE is not expected to affect endoproteolytic processing. In this report we have addressed the mechanism of this unexpected finding by directly examining the expression of the major precursor processing endoproteases, prohormone convertases PC1 and PC2 in Cpe fat mice. We found that the levels of PC1 and PC2 are differentially altered in a number of brain regions and in the pituitary. Since these enzymes have been implicated in the generation of neuroendocrine peptides (dynorphin A-17, ␤-endorphin, and ␣-melanocyte-stimulating hormone) involved in the control of feeding behavior and body weight, we compared the levels of these peptides in Cpe fat and wild type animals. We found a marked increase in the level of dynorphin A-17, a decrease in the level of ␣-melanocyte-stimulating hormone, and an alteration in the level of C-terminally processed ␤-endorphin. These results suggest that the impairment in the level of these and other peptides involved in body weight regulation is mainly due to an alteration in carboxypeptidase and prohormone convertase activities and that this may lead to the development of obesity in these animals.

show abstract

Section: Methodsmentioning

confidence: 99%

Impaired Prohormone Convertases in Cpe fat/Cpe fat Mice

Berman¹,

Mzhavia²,

Polonskaia³

et al. 2001

Journal of Biological Chemistry

View full text Add to dashboard Cite

show abstract

“…Thus, a concomitant decline in β-EP might actually tend to restore Pomc expression levels. Conversely, mu-opioid antagonism has been shown to stimulate Pomc gene expression and peptide release (17,25). Thus, both γ-MSH and β-EP may exert inhibitory effects on POMC via different inhibitory autoreceptors.…”

Section: Suppression Of Pomc Expression By [D-trp 8 ]-γ-Msh Is a Tranmentioning

confidence: 99%

Effects of selective modulation of the central melanocortin-3-receptor on food intake and hypothalamic POMC expression

et al. 2008

Self Cite

View full text Add to dashboard Cite

Hypothalamic POMC neurons regulate energy balance via interactions with brain melanocortin receptors (MC-Rs). POMC neurons express the MC3-R which can function as an inhibitory autoreceptor in vitro. We now demonstrate that central activation of MC3-R with icv infusion of the specific MC3-R agonist, [D-Trp 8 ]-γ-MSH, transiently suppresses hypothalamic Pomc expression and stimulates food intake in rats. Conversely, we also show that icv infusion of a low dose of a selective MC3-R antagonist causes a transient decrease in feeding and weight gain. These data support a functional inhibitory role for the MC3-R on POMC neurons that leads to changes in food intake.

show abstract

“…Protein content was determined by the Bradford method using BSA as the standard. In addition, the supernatant pooled from medial basal hypothalamus (MBH), brainstem, and cerebellum homogenates from three nontransgenic and three transgenic mice were chromatographed on G-75 Sephadex columns as described earlier, and the eluted fractions were assayed for ␣-MSH and ␥ 3 -MSH immunoactivity (33).…”

Section: Hair Total Melanin Contentmentioning

confidence: 99%

Metabolic Effects of Transgenic Melanocyte-Stimulating Hormone Overexpression in Lean and Obese Mice

et al. 2004

Self Cite

View full text Add to dashboard Cite

The proopiomelanocortin-derived peptide, alpha-MSH, inhibits feeding via melanocortin receptors in the hypothalamus and genetic defects inactivating the melanocortin system have been shown to lead to obesity in experimental animals and humans. To determine whether long-term melanocortinergic activation has significant effects on body weight and composition and insulin sensitivity, transgenic mice overexpressing N-terminal proopiomelanocortin, including alpha- and gamma(3)-MSH, under the control of the cytomegalovirus-promoter were generated. The transgene was expressed in multiple tissues including the hypothalamus, in which both alpha-MSH and gamma(3)-MSH levels were increased approximately 2-fold, compared with wild-type controls. Transgene homozygous mice were also crossed with obese leptin receptor-deficient db(3J) and obese yellow A(y) mice. MSH overexpression led to uniform, dose- dependent darkening of coat color. MSH overexpression reduced weight gain and adiposity and improved glucose tolerance in lean male mice. In female transgenic mice, there was no significant effect on body weight, but there was a significant decrease in insulin levels. Obesity was attenuated in obese db(3J)/db(3J) male and female mice, but there was no improvement in glucose metabolism. In contrast, the MSH transgene improved glucose tolerance in male A(y) mice. These results support the hypothesis that long-term melanocortinergic activation could serve as a potential strategy for anti-obesity and/or antidiabetic therapy.

show abstract

Effect of opioid antagonism on β-endorphin processing and proopiomelanocortin-peptide release in the hypothalamus

Cited by 27 publications

References 23 publications

Impaired Prohormone Convertases in Cpe fat/Cpe fat Mice

Impaired Prohormone Convertases in Cpe fat/Cpe fat Mice

Effects of selective modulation of the central melanocortin-3-receptor on food intake and hypothalamic POMC expression

Metabolic Effects of Transgenic Melanocyte-Stimulating Hormone Overexpression in Lean and Obese Mice

Contact Info

Product

Resources

About