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Expression and Function of Vasoactive Intestinal Peptide, Pituitary Adenylate Cyclase-Activating Polypeptide, and Their Receptors in the Human Adrenal Gland

Department of Human Anatomy and Physiology, Section of Anatomy, University of Padua, I-35121 Padua, Italy

Address all correspondence and requests for reprints to: Prof. G. G. Nussdorfer, Department of Human Anatomy and Physiology, Section of Anatomy, Via Gabelli 65, I-35121 Padova, Italy. E-mail: . gastone.nusdorfer{at}unipd.it

Abstract

VIP and pituitary adenylate cyclase-activating polypeptide (PACAP) are two regulatory peptides that possess remarkable amino acid sequence homology and act through common receptors, named PAC₁, VPAC₁, and VPAC₂. PAC₁ receptor is selective for PACAP, whereas VPAC₁ and VPAC₂ receptors bind both VIP and PACAP. We have investigated the expression and function of VIP, PACAP, and their receptors in the zona glomerulosa (ZG), zonae fasciculata and reticularis, and adrenal medulla (AM) of the human adrenal cortex. RT-PCR and RIA detected VIP and PACAP expression exclusively in AM cells. RT-PCR demonstrated the presence of PAC₁ mRNA only in AM and of VPAC₁ and VPAC₂ mRNAs in both ZG and AM cells. VIP and PACAP concentration-dependently increased aldosterone and catecholamine secretion from cultured ZG and AM cells. The catecholamine response to both peptides was higher than the aldosterone response, and the secretagogue action of PACAP was more intense than that of VIP. The aldosterone response of cultured ZG cells to VIP or PACAP was unaffected by the PAC₁ receptor antagonist PACAP-(6–38) (PAC₁-A), but was significantly decreased by the VPAC₁ receptor antagonist [Ac-His¹,D-Phe²,Lys¹⁵,Arg¹⁶]VIP-(3–7),GH-releasing factor-(8–27)-NH₂ (VPAC₁-A). The catecholamine response of cultured AM cells to VIP was lowered by VPAC₁-A and unaffected by PAC₁-A; conversely, the catecholamine response to PACAP was reduced by both PAC₁-A and VPAC₁-A. Simultaneous exposure to both antagonists did not abolish the catecholamine response to PACAP. Collectively, our findings allow us to conclude that in human adrenals 1) VIP and PACAP biosynthesis exclusively occurs in AM cells; 2) ZG cells are provided with functional VPAC₁ and VPAC₂ receptors, whose activation by VIP or PACAP elicits a moderate aldosterone response; 3) AM cells possess PAC₁, VPAC₁, and VPAC₂ receptors, whose activation evokes a marked catecholamine response; and 4) the catecholamine response to PACAP is more intense than that to VIP, because it is mediated by all subtypes of VIP/PACAP receptors.

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