Cerebellin stimulates the secretory activity of the rat adrenal gland: in vitro and in vivo studies

Cerebellin is a 16-aminoacid peptide widely distributed in the central nerv ous system, where it exerts neuromodulatory functions. Cerebellin is contai ned in human adrenal medulla, and it has been recently demonstrated that ce rebellin elicits catecholamine release by human adrenal in vitro. Aim of th e present study was to ascertain whether cerebellin affects adrenal functio n in the rat. Cerebellin concentration-dependently (from 10(-9) to 10(-7) M ) increased norepinephrine (but not epinephrine) and cyclic-AMP production by adrenomedullary tissue in vitro. The norepinephrine response to 10(-7) M cerebellin was blocked by the protein kinase (PK) A inhibitor H-89, but no t by the phospholipase C inhibitor U-73122 or the PKC inhibitor calphostin- C. Cerebellin did not affect aldosterone and corticosterone secretion of di spersed zona glomerulosa and zona fasciculata-reticularis adrenocortical ce lls. Cerebellin concentration-dependently (from 10(-8) to 10(-7) M) enhance d norepinephrine release by in situ perfused rat adrenals. Cerebellin (10(- 7) M) also elicited a significant rise in aldosterone and corticosterone ou tput. and this effect was annulled by either the pl-adrenoceptor antagonist I-alprenolol or H-89. Collectively, the present findings allow us to concl ude that cerebellin 1) directly stimulates norepinephrine release via the a denylate cyclase/PKA-dependent signaling pathway; and 2) indirectly enhance s adrenocortical secretion in vivo, through a paracrine mechanism involving medullary catecholamine release. (C) 2000 Harcourt Publishers Ltd.