Modulation of Opioid Receptor Binding by Cis and Trans Fatty Acids

Remmers, Ann E.; Nordby, Gordon L.; Medzihradsky, Fedor

doi:10.1111/j.1471-4159.1990.tb05787.x

Cited by 21 publications

(25 citation statements)

References 31 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In agreement with lacking regulation by GTP (4) have shown that the biphasic binding of this antagonist reflects interactions with both u (high-affinity component) and 6 (low-affinity component) opioid receptors (33). These interpretations are in line with the limited binding selectivity of NTX in brain (33,34).…”

Section: Resultssupporting

confidence: 68%

“…3) and opioid-sensitive GTPase activity. (29) and receptor coupling to low Km GTPase (30). Earlier it was shown that, after inactivation of opioid-sensitive adenylate cyclase in NG108-15 cells by N-ethylmaleimide, enzyme activity was restored by fusion of the hybrid cells and C6 glioma cells.…”

Section: Resultsmentioning

confidence: 99%

“…Guanine nucleotidedependent dissociation of the complex then yields the lowaffinity form of the ligand-occupied receptor. A preliminary report on these findings was presented recently (14). Isolated Membranes and Cell Culture.…”

mentioning

confidence: 95%

See 2 more Smart Citations

Reconstitution of high-affinity opioid agonist binding in brain membranes.

Remmers

Medzihradsky

1991

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

In synaptosomal membranes from rat brain (12,13).Although the results outlined above have implicated modulationt of ligand-receptor interaction by G proteins, they did not establish the molecular identity of the high-and lowaffinity components of opioid binding. In this study, we have directly linked high-affinity opioid agonist binding and opioid-sensitive GTPase activity to membrane G protein. Inactivation of G protein at high pH abolished high-affinity agonist, but not antagonist, binding. Guanine nucleotidesensitive high-affinity opioid binding and opioid-sensitive GTPase activity were restored after fusion of the alkalitreated synaptosomal brain membranes with membranes from opioid receptor-deficient, but inhibitory G proteincontaining, C6 glioma cells. The results describe high-affinity opioid agonist binding as a ternary complex composed of ligand, receptor, and G protein. Guanine nucleotidedependent dissociation of the complex then yields the lowaffinity form of the ligand-occupied receptor. A preliminary report on these findings was presented recently (14). Isolated Membranes and Cell Culture. The synaptosomal preparation was isolated from brain cortices ofmale SpragueDawley rats as described (15). Prior to their freezing at -80'C, the synaptosomes were disrupted in a Dounce homogenizer. MATERIALS AND METHODSTo reach confluence, the C6 glioma cells were grown as a monolayer in a minimal essential medium supplemented with 10% fetal bovine serum and 1% pyruvate for 8-9 days at 370C in 95% air/5% CO2. After detachment from the flask wall by incubation at 370C in saline, the cells were disrupted in hypotonic buffer with a Dounce homogenizer. The pelleted membranes were resuspended in 50 mM Tris HCl (pH 7.4) to a protein concentration of 1 mg/ml and were stored at -800C.Protein was determined according to Bradford (16)

show abstract

Section: Resultssupporting

confidence: 68%

Section: Resultsmentioning

confidence: 99%

See 1 more Smart Citation

Reconstitution of high-affinity opioid agonist binding in brain membranes.

Remmers

Medzihradsky

1991

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

show abstract

“…Although the molecular mechanisms elevating ENK and DYN transcripts in response to fat remain to be characterized, evidence demonstrates a direct stimulatory effect of short-chain fatty acids on ENK gene expression in PC12 rat cells via an intact PKA signaling pathway, with a possible involvement of lipid-activated transcription factors [52]. Fatty acids may also modulate the binding of opioid peptides to their receptor [53]. This evidence indicates that opioids in the PVN, as shown for GAL, are responsive to circulating lipids, TG or fatty acids, which may mediate the stimulatory effect of dietary fat on these peptides.…”

Section: Relation Of Opioid Peptides To Dietary Fatmentioning

confidence: 99%

Overconsumption of dietary fat and alcohol: Mechanisms involving lipids and hypothalamic peptides

Leibowitz

2007

Physiology & Behavior

View full text Add to dashboard Cite

The studies described in this report provide interesting animal models for exploring some of the metabolic and neural antecedents to the over-consumption of fat and alcohol. The results provide strong support for the existence of positive feedback loops that involve a close relation between circulating lipids and orexigenic peptides in dorsal regions of the hypothalamus. The peptides involved in these circuits include galanin, enkephalin, dynorphin and orexin. These peptides are expressed in the paraventricular nucleus and perifornical lateral hypothalamus, and they have very different functions from peptides expressed in the arcuate nucleus. Through mechanisms involving circulating lipids that rise on energy-dense diets, these peptides in the dorsal hypothalamus are each increased by the consumption of fat and ethanol; these nutrients, in turn, stimulate further production of these same peptides that promote overeating and excess drinking. These mechanisms involving non-homeostatic, positive feedback circuits may be required under conditions when food supplies are scarce and periods of gorging are essential to survival. However, they have pathological and sometimes life-threatening consequences in modern society, where fat-rich foods and alcoholic drinks are abundantly available and are contributing to the marked rise over the past 25 years in obesity and diabetes in both children and adults.

show abstract

“…Although the molecular mechanisms elevating ENK and DYN transcripts within 15 and 60 min remain to be characterized, evidence (44) demonstrates a direct stimulatory effect of short-chain fatty acids on ENK gene expression in PC12 rat cells via an intact PKA signaling pathway, with a possible involvement of lipid-activated transcription factors. It is of interest that, in addition to their effects on peptide expression, fatty acids may also modulate the binding of opioid peptides to their receptor (58).…”

Section: Stimulatory Effect Of Dietary Fat On Opioid Peptides In the mentioning

confidence: 99%

Dietary fat stimulates endogenous enkephalin and dynorphin in the paraventricular nucleus: role of circulating triglycerides

Chang

Karatayev²,

Ahsan³

et al. 2007

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Chang GQ, Karatayev O, Ahsan R, Gaysinskaya V, Marwil Z, Leibowitz SF. Dietary fat stimulates endogenous enkephalin and dynorphin in the paraventricular nucleus: role of circulating triglycerides. Am J Physiol Endocrinol Metab 292: E561-E570, 2007; doi:10.1152/ajpendo.00087.2006.-The opioid peptides enkephalin (ENK) and dynorphin (DYN), when injected into the hypothalamus, are known to stimulate feeding behavior and preferentially increase the ingestion of a high-fat diet. Studies of another peptide, galanin (GAL), with similar effects on feeding demonstrate that a high-fat diet, in turn, can stimulate the expression of this peptide in the hypothalamus. The present study tested different diets and variable periods of high-vs. low-fat diet consumption to determine whether the opioid peptides respond in a similar manner as GAL. In six experiments, the effects of dietary fat on ENK and DYN were examined in three hypothalamic areas: the paraventricular nucleus (PVN), perifornical hypothalamus (PFH), and arcuate nucleus (ARC). The results demonstrated that the ingestion of a high-fat diet increases gene expression and peptide levels of both ENK and DYN in the hypothalamus. The strongest and most consistent effect is seen in the PVN. In this nucleus, ENK and DYN are increased by 50 -100% after 1 wk, 1 day, 60 min, and even 15 min of high-fat diet consumption. While showing some effect in the PFH, these peptides in the ARC are considerably less responsive, exhibiting no change in response to the briefer periods of diet intake. This effect of dietary fat on PVN opioids can be observed with diets equal in caloric density and palatability and without a change in caloric intake, body weight, fat pad weight, or levels of insulin or leptin. The data reveal a strong and consistent association between these peptides and a rise in circulating levels of triglycerides, supporting a role for these lipids in the fat-induced stimulation of opioid peptides in the PVN, similar to GAL. galanin; opioid peptides; arcuate nucleus; feeding behavior; lipids RECENT EVIDENCE has demonstrated a close relationship between the orexigenic peptide galanin (GAL) and the consumption of a fat-rich diet. When injected into the paraventricular nucleus (PVN), this peptide stimulates feeding behavior in rats, and while having no specific effect on macronutrient preferences, GAL produces its strongest response in animals that prefer fat or are maintained on a fat-rich diet (34,41,65). Moreover, measurements of endogenous GAL reveal a stimulatory effect of acute or chronic high-fat diet consumption on gene expression and peptide levels specifically in the PVN (13,36,52). This supports the existence of a positive feedback loop, whereby a peptide stimulates intake of a diet that, in turn, increases production of this same peptide.The focus of this study is on the endogenous opioid peptides, enkephalin (ENK) and dynorphin (DYN). These peptides, like GAL, are known to increase feeding in a dose-dependent manner, and this response is observed with injection in...

show abstract

Modulation of Opioid Receptor Binding by Cis and Trans Fatty Acids

Cited by 21 publications

References 31 publications

Reconstitution of high-affinity opioid agonist binding in brain membranes.

Reconstitution of high-affinity opioid agonist binding in brain membranes.

Overconsumption of dietary fat and alcohol: Mechanisms involving lipids and hypothalamic peptides

Dietary fat stimulates endogenous enkephalin and dynorphin in the paraventricular nucleus: role of circulating triglycerides

Contact Info

Product

Resources

About