The action of the regulatory neuropeptides vasoactive intestinal polypeptide (VIP) and pituitary adenylate cyclase-activating polypeptide (PACAP) carries out through the shared receptors VPAC1 and VPAC2 and the exclusive PACAP receptor PAC1, all of which are G protein-coupled receptors. Formerly, we showed that the administration of both peptides enhance catecholamine, corticosterone and aldosterone release from adrenal cell co-culture. Further, the distribution of VIP and PACAP receptors in the adrenal glands of the Italian wall lizard, Podarcis sicula, was previously demonstrated: VPAC1 was found within steroidogenic tissue, VPAC2 and PAC1 within chromaffin tissue. In the present study we investigated the c-AMP signaling pathway involved in the VIP and PACAP-induced secretion of adrenal cell co-cultures. Using VPAC1 antagonist [Ac-His1, D-Phe2,Lys15,Arg16]VIP-(3-7),GH-releasing factor-(8-27)-NH2 (VPAC1-A), the PAC1 antagonist PACAP6-38 (PAC1-A) and VPAC2 immunoneutralized cells, in in vitro VIP or PACAP treated adrenal cell co-cultures, we showed that the VIP- and PACAP-induced steroid and peptide hormone secretion is carried out through the activation of selective receptors which promote, in time dependent manner, the production of c-AMP: after 1 h of PACAP/VPAC1-A/VPAC2 immunoneutralized cells treatment, c-AMP production is 250% in relation to control. After 3 h of stimulation with VIP/PAC1-A/VPAC2 immunoneutralized cells, the c-AMP production was increased of 281% compared with control. After 24 h of treatment neither VIP nor PACAP was able to stimulate c-AMP production. Further, we showed that VIP enhances c-AMP production through the binding of the VPAC1 receptor and PACAP increases c-AMP production through the interaction with the PAC1 receptor exclusively. Thus, our investigation showed that the activation of adenylate-cyclase is required to permit the in vitro VIP and PACAP stimulation and PACAP is faster than VIP to induce c-AMP production in lizard adrenal cell secretion.
03 - 07 May 2008
European Society of Endocrinology