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.
Neuropeptides B and W (NPB and NPW) are regulatory peptides that act via two subtypes of G protein-coupled receptors, named GPR7 and GPR8. RT-PCR demonstrated the expression of these receptors in both zona glomerulosa and zona fasciculata-reticularis (ZF/R) cells of the human adrenal cortex. NPB and NPW did not affect aldosterone secretion from dispersed zona glomerulosa cells but enhanced cortisol production from ZF/R cells, NPB being more effective than NPW. NPB evoked sizable cAMP and inositol triphosphate responses from ZF/R cells, which were abrogated by the adenylate cyclase inhibitor SQ-22536 and the phospholipase C inhibitor U-73122, respectively. Cortisol response to NPB was lowered by either SQ-22536 and the protein kinase (PK) A inhibitor H-89 or U-73122 and the PKC inhibitor calphostin-C and abolished by the simultaneous exposure to H-89 and calphostin-C. NPW elicited only a rise in cAMP production from dispersed ZF/R cells, and its cortisol response was suppressed by both SQ-22536 and H-89. PreproNPB and preproNPW mRNAs were detected in human adrenal cortexes. We conclude that: 1) NPB and NPW exert a secretagogue action on human ZF/R cells, probably acting in an autocrine-paracrine manner; and 2) the effect of NPB is mediated by both the adenylate cyclase/PKA and the phospholipase C/PKC cascades, whereas that of NPW involves only the activation of the former signaling pathway.
Mazzocchi
G
G
Department of Human Anatomy and Physiology, Section of Anatomy, University of Padova, Via Gabelli 65, I-35121 Padova, Italy.
Rebuffat
P
P
Ziolkowska
A
A
Rossi
G P
GP
Malendowicz
L K
LK
Nussdorfer
G G
GG
D000262:Adenylyl Cyclases / Q000378:metabolism*; D000302:Adrenal Cortex / Q000502:physiology*; D000450:Aldosterone / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D017931:DNA Primers; D006801:Humans; D006854:Hydrocortisone / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D013252:Steroid 11-beta-Hydroxylase / Q000235:genetics; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D010738:Type C Phospholipases / Q000378:metabolism*; D015383:Zona Fasciculata / Q000502:physiology; D015384:Zona Glomerulosa / Q000502:physiology; D015385:Zona Reticularis / Q000502:physiology
D017931:DNA Primers; C485722:NPBWR1 protein, human; C401923:NPBWR2 protein, human; C467731:NPW protein, human; D009479:Neuropeptides; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D018013:Receptors, Neuropeptide; C495188:neuropeptide B; D000450:Aldosterone; D000242:Cyclic AMP; D013254:Steroid 17-alpha-Hydroxylase; D013252:Steroid 11-beta-Hydroxylase; D010738:Type C Phospholipases; D000262:Adenylyl Cyclases; D006854:Hydrocortisone