G Protein Receptors 7 and 8 Are Expressed in Human Adrenocortical Cells, and Their Endogenous Ligands Neuropeptides B and W Enhance Cortisol Secretion by Activating Adenylate Cyclase- and Phospholipase C-Dependent Signaling Cascades

Abstract. Neuropeptides B and W (NPB and NPW) have been identified as endogenous ligands of the G protein-coupled receptors (GPR) 7 and 8, which in humans are expressed in the hypothalamus and probably involved in the regulation of energy homeostasis and feeding behavior. GPR8 is absent in the rat, where the GPR8-like receptor (GPR8-LR) has been described. Reverse transcription-polymerase chain reaction detected the expression of NPB, NPW, GPR7 and GPR8-LR mRNAs in the hypothalamus, anterior pituitary, thyroid and parathyroid glands, pancreatic islets, adrenal glands, ovary and testis of the rat. Immunocytochemistry demonstrated the presence of NPB and NPW immunoreactivities in these same glands. Radioimmune assay showed that the bolus intraperitoneal injection of 2 nmol/100 g NPB or NPW raised the plasma levels of parathyroid hormone, corticosterone and testosterone. NPB also increased the blood concentration of thyroxine, and NPW that of ACTH and estradiol. Taken together, these findings allow us to suggest that NPB and NPW play a role in the autocrine-paracrine functional regulation of the endocrine system in the rat.

Section: Discussionsupporting

confidence: 92%

Expression of neuropeptides B and W and their receptors in endocrine glands of the rat

Hochol¹,

Belloni²,

Ruciński³

et al. 2006

“…As demonstrated, NPB activates and binds to both human NPBWR1 (with higher affinity) and NPBWR2, and similar effects are demonstrated with NPW23 and NPW30, with NPBWR1 binding with lower affinity (6,8). Previous observations revealed notable differences in NPB and NPW action on both rat and human adrenocortical cells (18,20,24). Present data on leptin and insulin regulation by NPB and NPW extend these earlier observations to include differences in the biological activity of both neuropeptides.…”

Section: Discussionsupporting

confidence: 82%

“…Concerning the functional role of the NPB-NPW system, a growing body of evidence indicates that this system is involved in the regulation of neuroendocrine axis activity. This suggestion is confirmed by findings demonstrating that NPB or NPW evoked secretion of anterior pituitary and adrenocortical hormones in vivo (5,10,18,20,(22)(23)(24).…”

Section: Discussionsupporting

confidence: 62%

“…Both at the level of mRNA and protein, expression of NPB and NPW and their receptors in human and rat endocrine glands and hypothalamus have been well documented (6,(16)(17)(18)(19)(20)(21). Concerning the functional role of the NPB-NPW system, a growing body of evidence indicates that this system is involved in the regulation of neuroendocrine axis activity.…”

Section: Discussionmentioning

confidence: 99%

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Neuropeptide W exerts a potent suppressive effect on blood leptin and insulin concentrations in the rat

Ruciński

Nowak²,

Chmielewska³

et al. 2007

Abstract. Neuropeptide B/W receptor 1 (NPBWR1) and neuropeptide B/W receptor 2 (NPBWR2) are two structurally related orphan receptors linked to protein G. In rodents NPBWR2 is absent, and its counterpart is described as being similar to neuropeptide B/W receptor 2. Endogenous ligands of these receptors have been identified. One of them is 29 amino acid residues long, uniquely modified with bromine and, thus, termed neuropeptide B (NPB). The other, neuropeptide W (NPW), has been identified in two molecular forms of 23 and 30 amino acids (NPW23 and NPW30), respectively. Both NPB and NPW affect food intake and energy expenditure. Since leptin, a potent anti-obesity hormone, and insulin are involved in the control of energy homeostasis, the present study aimed to investigate whether NPB and NPW affect leptin and insulin secretion in the rat. RT-PCR technique revealed the presence of ppNPB, ppNPW, NPBWR1 and NPBWR2-like mRNAs in isolated pancreatic islets of the rat. NPB and NPW immunoreactivities were observed in all of the cells of the pancreatic islets. Only when a higher dose was administered (3 nmol/100 g body weight) did NPW transiently lower blood insulin levels whereas NPB injection did not alter insulinaemia in the studied rats. At 30 min, but not 60, of the experiment, NPW notably lowered blood leptin concentrations at both tested doses. On the contrary, NPB injections had no effect on blood leptin and insulin concentrations. Thus, the results suggest that NPW but not NPB exerts a potent suppressive effect on blood leptin concentrations in the rat, and this mechanism may be involved in NPW regulation of energy homeostasis.

“…cAMP and IP3 production. In the case of cAMP assay, the phosphodiesterase inhibitor IBMX (10 -4 M) was added to prevent cAMP metabolism (23). cAMP was extracted by incubating the medium with 0.1 N HCl for 20 min at 4˚C.…”

Section: Gal-r Immuno-blockadementioning

confidence: 99%

Galanin enhances corticosterone secretion from dispersed rat adrenocortical cells through the activation of GAL-R1 and GAL-R2 receptors coupled to the adenylate cyclase-dependent signaling cascade

Andreis

Malendowicz²,

Rebuffat³

et al. 2007

Abstract. Galanin is a regulatory peptide, which acts via three subtypes of receptors, named GAL-R1, GAL-R2 and GAL-R3. Reverse transcription-polymerase chain reaction demonstrated the expression of GAL-R1 and GAL-R2, but not GAL-R3 mRNAs in dispersed rat adrenal zona fasciculatareticularis (inner) cells. The immuno-blockade of GAL-R1 and GAL-R2, but not GAL-R3, decreased the binding of [ 3 H]galanin to dispersed cells, a complete inhibition being obtained only by the simultaneous blockade of both receptor subtypes. Galanin stimulated corticosterone and cyclic-AMP release from dispersed inner rat adrenocortical cells, while inositol triphosphate production was not affected. Again these responses to galanin were reversed by both the GAL-R1 and GAL-R2, but not the GAL-R3 immuno-blockade. The adenylate cyclase inhibitor SQ-22536 and the protein kinase (PK) A inhibitor H-89 abolished the corticosterone response of dispersed cells to galanin, while the phospholipase C inhibitor U-73122 and the PKC inhibitor calphostin-C were ineffective. We conclude that rat inner adrenocortical cells express GAL-R1 and GAL-R2 as mRNA and protein, and galanin stimulates corticosterone secretion acting via these receptor subtypes which are both coupled to the adenylate cyclase/PKA-dependent signaling pathway.