2423 Activation of ascending pathways from the nucleus of the solitary tract to the subfornical organ by hemorrhage

Abstract

We studied whether specific receptors for endothelin (ET) isopeptide exist in human aldosterone-producing adenoma and normal adrenal cortex, and whether ET isopeptides are produced by human adrenal gland. Competitive binding studies using [125I]ET-1 as a radioligand revealed the presence of a single class of high-affinity binding sites for ET-1 with the apparent Kd of 70 ± 31 pM and Bmax of 226 ± 139 fmol/mg protein in adenoma membranes almost comparable to those in adjacent normal cortex. The apparent Ki for ET-2 and ET-3 were 89 ± 33 pM and 82 ± 16 pM, respectively. Northern blot analysis of poly(A)+ RNA of adenoma and adjacent normal cortex using cDNAs for ET receptor subtype (ETa, ETb) and ET isopeptide (ET-1, ET-3) as probes revealed that ETa and ETb receptors as well as ET isopeptides (prepro-ET-1, preproET-3) are concomitantly expressed in both tissues.Our data demonstrate for the first time that ET receptor subtype (ETa and ETb) and ET isopeptide (ET-1 and ET-3) are concomitantly expressed by human adrenal cortex, suggesting the potential role of ETs as a local mediator in human adrenal gland.