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A novel peptide Ghrelin, found to be a ligand to growth hormone (GH) secretagogue receptor (GHS-R), exeterts to stimulates GH release from pituitary gland. Recently, it has been shown that ghrelin and its receptor are existed in a adrenal ground. At concentrations of 10nM and over (10nM, 100nM, and 1 µM), ghrelin significantly inhibited basal dopamine release by 30, 32 and 34%, respectively (P < 0.05) in PC12 cells, suggesting that ghrelin may be involved in the mechanism of catecholamine regulation in chromaffin cells. [ABSTRACT FROM AUTHOR]

Abstract: Recently, the insulin-sensitizing adipokine adiponectin and the insulin resistance-inducing adipokine tumor necrosis factor-α (TNF-α) were reported to inhibit each other''s production in adipocytes. We investigated the effects of two β3-adrenoceptor agonists, 5-[(2R)-2-[[(2R)-2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]-1,3-benzodioxole-2,2-dicarboxylate (CL-316,243) and (±)-(R⁎,R⁎)-[4-[2-[[2-(3-chlorophenyl)-2-hydroxyethyl]amino]propyl]phenoxy]acetic acid (BRL37344), on the gene expression of adiponectin, two adiponectin receptors, and TNF-α in adipose tissues of C57BL/6J mice. CL-316,243 and BRL37344 downregulated adiponectin, but upregulated adiponectin receptor 2 (not receptor 1) in epididymal or/and subcutaneous white adipose tissues and in brown adipose tissue. TNF-α expression was upregulated only in epididymal adipose tissue. To further explore these effects, we treated differentiated 3T3-L1 adipocytes with the non-selective β-adrenoceptor agonist isoproterenol. As a result, adiponectin receptor 2 (but not receptor 1) gene expression and TNF-α protein expression increased, but gene expression and secretion of adiponectin decreased. The upregulation of adiponectin receptor 2 by isoproterenol is most likely via β2,β3-adrenoceptors, adenylyl cyclases, and protein kinase A (PKA). However, the accompanying activation of AMP-activated protein kinase (AMPK) may inhibit this upregulation. Our results suggest that upregulation of TNF-α and downregulation of adiponectin by β-adrenoceptor activation may contribute to the pathogenesis of catecholamine-induced insulin resistance, and that upregulation of adiponectin receptor 2 may be a feedback result of reduced adiponectin. [Copyright &y& Elsevier]

Abstract: Urocortin is a novel mammalian member of the corticotrophin releasing factor (CRF)-related peptides. We have investigated the expression, mechanism of action and second messenger for urocortin in rat pheochromocytoma PC12 cells. We initially confirmed the expression of urocortin and CRF-R2β, which is thought to be an endogenous receptor for urocortin, in PC12 cells. We also demonstrate that urocortin (≥1nM) significantly elevates the level of cAMP in these cells. Moreover, α-helical CRF-(9-41), a more specific antagonist of CRF-R2 than CRF-R1 and the adenylate cyclase inhibitor SQ22536, inhibited the urocortin-induced increase in the level of cAMP. Thus, urocortin may exert its physiological role in chromaffin cells via CRF-R2β coupling to adenylate cyclase. Urocortin (≥1nM) significantly increased the mRNA level and activity of tyrosine hydroxylase (TH), a rate-limiting enzyme in the biosynthesis of catecholamine. Furthermore, urocortin-induced changes in TH-mRNA and activity were inhibited by H89 (a PKA inhibitor) and SQ22536 as well as α-helical CRF-(9-41). However, urocortin did not affect DNA synthesis or catecholamine secretion in these cells. In conclusion, we have demonstrated that urocortin stimulates catecholamine biosynthesis via the cAMP/protein kinase A pathway in PC12 cells, where both urocortin and its receptor, CRF-R2, are expressed. [Copyright &y& Elsevier]

We examined the effect of prolactin-releasing peptide (PrRP) on catecholamine secretion and DNA synthesis in rat pheochromocytoma PC12 cells. We initially confirmed the expression of both PrRP and its receptor in PC12 cells. PrRP31 and PrRP20 (≥10 nM) significantly increased dopamine secretion from PC12 cells. However, PrRP20-stimulated dopamine secretion was markedly weaker than that of PrRP31. Both EDTA (extracellular Ca2+ chelator) and BAPTA-AM (intracellular Ca2+ chelator) effectively suppressed PrRP31 (100 nM)-induced dopamine secretion. PrRP31and PrRP20 (≥1 nM) significantly induced an increase in the level of cAMP. The PKA inhibitor H89 (at 10 μM) impeded PrRP31- and PrRP20-induced dopamine secretion. Finally, we confirmed that PrRP did not affect DNA synthesis. These results indicate that PrRP may regulate catecholamine secretion but not the mitogenic effects in chromaffin cells. [Copyright &y& Elsevier]