Central mu, delta, and kappa opioid binding sites, and brain and pituitary beta-endorphin and met-enkephalin in genetically obese (ob/ob) and lean mice

doi:10.1016/0024-3205(89)90337-8

Life Sciences

Volume 44, Issue 16, 1989, Pages 1097-1105

https://doi.org/10.1016/0024-3205(89)90337-8 Get rights and content

Abstract

The equilibrium dissociation constants and maximal binding capacities of ³H-dihydromorphine (DHM), ³H-D-Ala²-D-leu³ -enkephalin (DADL), and ³H-dynorphin A(1–8) for their respective mu, delta, and kappa opiate binding sites were studied in brain membrane preparations from lean and genetically obese-hyperglycaemic (Aston ob/ob) mice. The concentration of kappa binding sites was 2.7 fold higher in obese compared with lean mouse brain ( $231_{±} 44.6 versus 83.3±10.3 fmoles^{3} H-dynorphin/mg protein respectively. mean ± SEM$ ). The concentration of delta binsing sites in obese was 1.6 fold that in lean mouse brain ( $94.5±8.6 vesus 59.5±6.5 fmoles^{3} H-DADL/mg protein$ ). In contrast, the concentration of brain mu receptors was 40% lower in obese compared with lean mice ( $20.8±2.19 and 34.8±3.1 fmoles^{3} H-DHM/mg protein respectively$ ). Binding affinities of delta and kappa sites for their respective ligands were not significantly different inlean V. obese mice. However, for mu sites, lean mouse binding data showed two affinities, one was not significantly different from obese (0.35nM) the second was lower (1.18nM) for DHM. Increases of approximately 5 fold and 3 fold in the brain content of beta-endorphin and met-enkephalin respectively, and no differences in brain dynorphin levels, were demonstrated in obese mice compared with lean controls. In obese mice, pituitary beta-endorphin content was 9 fold higher, met-enkephalin 4 fold higher and dynorphin 12 fold higher than in lean mice. The striking differences in opioid binding-site characteristics and in endogenous opioid peptide levels in obese compared with lean mice may contribute to the hyperphagia and, directly or indirectly, to the development of hyperglycaemia and hyperinsulinaemia in obese mice.

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Leptin plays a role in many processes, including weight regulation [4], POMC production [33], obesity [34], diabetes [35,36], glucocorticoids [37], endogenous opioids [38] and endocannabinoids [12]. Obesity and diabetes have been associated with altered nociception in humans and rodents [1,3], as have glucocorticoids [39], endogenous opioids [40] and endocannabinoids [27]). One possible method of leptin's action is through POMC.
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Central mu, delta, and kappa opioid binding sites, and brain and pituitary beta-endorphin and met-enkephalin in genetically obese (ob/ob) and lean mice

Abstract

Physiol. Reviews

Int. J. Obesity

Neurosci. Biobehave. Rev.

Am. J. Clin. Nutr.

Soc. Neurosci. Abstr.

Eur. J. Pharmacol.

Soc. Neurosci. Abstr.

Neuropharmacology

Life Sci.

Pharmacol. Biochem. Behav.

Peptides

Science

Peptides

Life Sci.