PMID- 10022429 OWN - NLM STAT- MEDLINE DCOM- 19990225 LR - 20181201 IS - 0021-972X (Print) IS - 0021-972X (Linking) VI - 84 IP - 2 DP - 1999 Feb TI - Cerebellin enhances in vitro secretory activity of human adrenal gland. PG - 632-5 AB - Cerebellin is a 16-amino acid peptide, originally isolated from rat cerebellum, whose presence has been recently demonstrated in the human adrenal glands and especially in medullary chromaffin cells. Cerebellin concentration dependently increased basal catecholamine (norepinephrine and epinephrine) release by human adrenal slices, containing medullary chromaffin tissue, minimal and maximal effective concentrations being 10(-9) and 10(-7) mol/L. Cerebellin (10(-7) mol/L) markedly enhanced cAMP release by adrenal slices, and the protein kinase A inhibitor H-89 (10(-5) mol/L) blocked catecholamine response to cerebellin. Cerebellin did not affect basal steroid secretion of dispersed human adrenocortical cells, but it concentration dependently increased aldosterone and cortisol production by adrenal slices. Again minimal and maximal effective concentrations were 10(-9) and 10(-7) mol/L. Aldosterone and cortisol responses to 10(-7) mol/L cerebellin was suppressed by both the beta-adrenoceptor antagonist l-alprenolol (10(-6) mol/L) and H-89 (10(-5) mol/L). Collectively, the present findings allow us to conclude that 1) cerebellin exerts a sizable secretagogue action on both cortex and medulla of human adrenals; 2) the peptide directly stimulates catecholamine release via the adenylate cyclase/protein kinase A-dependent signaling pathway; and 3) the mechanism underlying the adrenocortical stimulatory effect of cerebellin is indirect and probably involves the release of catecholamines, which in turn, acting in a paracrine manner, enhance steroid-hormone secretion. FAU - Mazzocchi, G AU - Mazzocchi G AD - Department of Human Anatomy, University of Padua, Italy. FAU - Andreis, P G AU - Andreis PG FAU - De Caro, R AU - De Caro R FAU - Aragona, F AU - Aragona F FAU - Gottardo, L AU - Gottardo L FAU - Nussdorfer, G G AU - Nussdorfer GG LA - eng PT - Journal Article PL - United States TA - J Clin Endocrinol Metab JT - The Journal of clinical endocrinology and metabolism JID - 0375362 RN - 0 (Adrenergic alpha-Antagonists) RN - 0 (Enzyme Inhibitors) RN - 0 (Isoquinolines) RN - 0 (Nerve Tissue Proteins) RN - 0 (Sulfonamides) RN - 4964P6T9RB (Aldosterone) RN - 877K5MQ27W (Alprenolol) RN - 94071-26-8 (cerebellin) RN - E0399OZS9N (Cyclic AMP) RN - EC 2.7.11.11 (Cyclic AMP-Dependent Protein Kinases) RN - M876330O56 (N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide) RN - WI4X0X7BPJ (Hydrocortisone) RN - X4W3ENH1CV (Norepinephrine) RN - YKH834O4BH (Epinephrine) SB - IM MH - Adrenal Cortex/drug effects/metabolism MH - Adrenal Glands/*drug effects/*metabolism MH - Adrenal Medulla/drug effects/metabolism MH - Adrenergic alpha-Antagonists/pharmacology MH - Adult MH - Aldosterone/metabolism MH - Alprenolol/pharmacology MH - Cyclic AMP/metabolism MH - Cyclic AMP-Dependent Protein Kinases/antagonists & inhibitors MH - Enzyme Inhibitors/pharmacology MH - Epinephrine/metabolism MH - Humans MH - Hydrocortisone/metabolism MH - In Vitro Techniques MH - Isoquinolines/pharmacology MH - Nerve Tissue Proteins/*pharmacology MH - Norepinephrine/metabolism MH - *Sulfonamides EDAT- 1999/02/18 00:00 MHDA- 1999/02/18 00:01 CRDT- 1999/02/18 00:00 PHST- 1999/02/18 00:00 [pubmed] PHST- 1999/02/18 00:01 [medline] PHST- 1999/02/18 00:00 [entrez] AID - 10.1210/jcem.84.2.5462 [doi] PST - ppublish SO - J Clin Endocrinol Metab. 1999 Feb;84(2):632-5. doi: 10.1210/jcem.84.2.5462.