Effect of Pituitary Adenylate Cyclase- Activating Polypeptide (PACAP) on Tyrosine Hydroxylase Gene Expression in the Rat Adrenal Medulla

International audienceI t is well known that the secretion of catecholamine by adrenal medullary cells is under the regulation of neurotransmitters, mainly acetylcholine. During the last years, the localization of peptides and peptidergic receptors in the adrenal medulla has raised the possibility of a peptidergic regulation of catecholamine secretion by adrenal chromaffin cells. For example, we have recently shown that neuropeptide Y can increase mRNA levels of tyrosine hydroxylase (TH), the enzyme that catalyzes the first step in the biosynthe-sis of catecholamines in the rat adrenal medulla. 1 Adenylate cyclase-activating polypeptide (PACAP), a 38 amino acid polypeptide isolated from the ovine hypothalamus on the basis of its stimulatory effect on cAMP production by pituitary cells, 2 has been found in the brain and peripheral organs, particularly the gastrointestinal tract, testis, and adrenal medulla. 3-5 The occurrence of PACAP receptors (type 1) in the rat adrenal medulla 6 and the stimulating influence of PACAP on the release of catecholamines from cultured porcine adrenal chromaffin cells 7 strongly suggest that this peptide might play a role in the control of catecholamine secretion by the adrenal medulla. In order to study the possible involvement of PACAP in the regulation of catecholamine biosynthesis by the adrenal gland, we have studied the effects of intravenous injections of PACAP and its potent antagonist PACAP(6-38) 8 on the genetic expression of TH in the adrenal medulla of the adult intact male rat. To determine the site of action of PACAP, we performed bilateral adrena-lectomy and homologous implantation of the adrenals under the kidney capsules. Those animals with implanted adrenals were injected with the same peptides. In all the experiments, eight animals per group were used. The levels of TH mRNA levels were measured by quantitative in situ hybridization. The hybridization technique was performed as previously described. 1 The hybridized sections were exposed to Kodak X-Oma