endomorphin-1 has been researched along with Hypertension* in 1 studies
1 other study(ies) available for endomorphin-1 and Hypertension
| Article | Year |
|---|---|
GPCR dimerization in brainstem nuclei contributes to the development of hypertension.
μ-Opioid receptors, pro-opiomelanocortin and pro-enkephalin are highly expressed in the nucleus tractus solitarii (NTS) and μ receptor agonists given to the NTS dose-dependently increased BP. However, the molecular mechanisms of this process remain unclear. In vitro, μ receptors heterodimerize with α2A -adrenoceptors. We hypothesized that α2A -adrenoceptor agonists would lose their depressor effects when their receptors heterodimerize in the NTS with μ receptors.. We microinjected μ-opioid agonists and antagonists into the NTS of rats and measured changes in BP. Formation of μ receptor/α2A -adrenoceptor heterodimers was assessed with immunofluorescence and co-immunoprecipitation methods, along with proximity ligation assays.. Immunofluorescence staining revealed colocalization of α2A -adrenoceptors and μ receptors in NTS neurons. Co-immunoprecipitation revealed interactions between α2A -adrenoceptors and μ receptors. In situ proximity ligation assays confirmed the presence of μ receptor/α2A -adrenoceptor heterodimers in the NTS. Higher levels of endogenous endomorphin-1 and μ receptor/α2A -adrenoceptor heterodimers were found in the NTS of hypertensive rats, than in normotensive rats. Microinjection of the μ receptor agonist [D-Ala(2) , MePhe(4) , Gly(5) -ol]-enkephalin (DAMGO), but not that of the α2A -adrenoceptor agonist guanfacine, into the NTS of normotensive rats increased μ receptor/α2A -adrenoceptor heterodimer formation and BP elevation. The NO-dependent BP-lowering effect of α2A -adrenoceptor agonists was blunted following increased formation of μ receptor/α2A -adrenoceptor heterodimers in the NTS of hypertensive rats and DAMGO-treated normotensive rats.. Increases in endogenous μ receptor agonists in the NTS induced μ receptor/α2A -adrenoceptor heterodimer formation and reduced the NO-dependent depressor effect of α2A -adrenoceptor agonists. This process could contribute to the pathogenesis of hypertension. Topics: Adrenergic alpha-2 Receptor Agonists; Analgesics, Opioid; Animals; Blood Pressure; Brain Stem; Dimerization; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Hypertension; Male; Microinjections; Narcotic Antagonists; Oligopeptides; Protein Multimerization; Rats; Rats, Inbred SHR; Receptors, Adrenergic, alpha-2; Receptors, Opioid, mu; Solitary Nucleus | 2015 |