title: Effect of the triakontatetraneuropeptide (TTN) on corticosteroid secretion by the frog adrenal gland.
abstract: Diazepam-binding inhibitor (DBI) was initially isolated from the rat brain as a result of its ability to compete with benzodiazepines for their receptors. Immunohistochemical studies have recently shown the presence of peripheral-type benzodiazepine receptor (PBR)- and DBI-like immunoreactivity in the frog adrenal gland. The aim of the present study was to investigate the effect of two biologically active DBI-derived peptides, the triakontatetraneuropeptide [TTN; DBI(17-50)] and the octadecaneuropeptide [ODN; DBI(33-50)], on corticosteroid secretion by frog adrenocortical cells. Exposure of frog adrenal explants to graded concentrations of TTN (3.16 x 10(-8) to 3.16 x 10(-6) M) induced a dose-related increase in corticosterone and aldosterone secretion. In contrast, ODN did not modify corticosteroid output. When repeated pulses of TTN (10(-6) M) were administered at 2-h intervals, the response of the adrenal explants to the second dose of TTN was markedly reduced, suggesting the existence of a desensitization phenomenon. Exposure of dispersed adrenal cells to TTN also induced a marked stimulation of corticosteroid secretion, indicating that TTN acts directly on adrenocortical cells. The central-type benzodiazepine receptor (CBR) agonist, clonazepam, did not stimulate corticosteroid secretion and the CBR antagonist, flumazenil, did not block the stimulatory action of TTN. Similarly, the PBR agonist, Ro5-4864, did not mimic the stimulatory effect of TTN and the PBR antagonist, flunitrazepam, did not affect the stimulatory action of TTN. The present study provides the first evidence for a stimulatory effect of TTN on intact adrenocortical cells. The receptor mediating the corticotropic action of TTN is not related to central- or peripheral-type benzodiazepine receptors. Our data suggest that TTN, released by chromaffin cells, may act as a paracrine factor regulating the activity of adrenocortical cells.
authors.affiliation: European Institute for Peptide Research (IFRMP No. 23), INSERM U 413, UA CNRS, University of Rouen, Mont-Saint-Aignan, France.
authors.forename: O
authors.initials: O
authors.lastname: Lesouhaitier
authors.forename: M
authors.initials: M
authors.lastname: Feuilloley
authors.forename: H
authors.initials: H
authors.lastname: Vaudry
mesh_terms: D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000311:Adrenal Glands / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002352:Carrier Proteins / Q000276:immunology; D019439:Chromaffin Cells / Q000187:drug effects / Q000378:metabolism; D003429:Cross Reactions; D026261:Diazepam Binding Inhibitor; D007106:Immune Sera; D066298:In Vitro Techniques; D008297:Male; D009479:Neuropeptides / Q000276:immunology / Q000494:pharmacology*; D010446:Peptide Fragments / Q000276:immunology / Q000494:pharmacology*; D011895:Rana ridibunda; D011963:Receptors, GABA-A / Q000187:drug effects
chemical_list: D000305:Adrenal Cortex Hormones; D002352:Carrier Proteins; D026261:Diazepam Binding Inhibitor; D007106:Immune Sera; D009479:Neuropeptides; D010446:Peptide Fragments; D011963:Receptors, GABA-A; C060941:triakontatetraneuropeptide