Regulatory Peptides, 48 (1993) 381-388 381 © 1993 Elsevier Science Publishers B.V. All rights reserved 0167-0115/93/$06.00 REGPEP 01543 Adrenalectomy reduces atrial natriuretic peptide stimulated guanylate cyclase activity in rat paraventricular nucleus Anita Israel*, Yaira Mathison, Maria Cierco, Maria del Rosario Garrido and Yarisma Barbella Faculty of Pharmao', Department of Biological Science, Universidad Central de Venezuela, Apartado Postal 50176, Sabana Grande 1050 A, Caracas (Venezuela) (Received 12 May 1992; revised version received 25 April 1993; accepted 3 June 1993) Key words: Atrial natriuretic peptide; Guanylate cyclase; cGMP; Adrenalectomy Summary Atrial natriuretic peptide (ANP) or an Atriopeptin III analog (PL 058) stimulated cGMP formation in the membrane fraction of rat olfactory bulb, median eminence and paraventricular nucleus, in a dose-dependent manner. The effect of the Atriopeptin III analog was 20-40~o greater than that of ANP. Bilateral adrenalec- tomy, with or without mineralo- or glucocorticoid-replacement, on ANP-stimulated cGMP formation was in- vestigated in rat paraventricular nucleus. 11 days after bilateral adrenalectomy a reduced responsiveness to ANP- or PL 058-induced cGMP production was observed. This effect was prevented by deoxycorticosterone, but not by dexamethasone administration. Our results further support the presence ofguanylate cyclase-coupled ANP receptors in brain localized target sites; and they provide evidence suggesting that guanylate cyclase-linked ANP binding sites in the PVN are susceptible to regulatory changes after adrenalectomy-induced activation of the hypothalamus-hypophyso- adrenocortical system. Introduction Atrial natriuretic peptide (ANP) is a hormone pro- duced by the heart and released into general circu- lation [ 1,2]. This peptide acts on specific receptors *Corresponding author. Fax: + 58 2662 6027. located in kidney, adrenal gland and vascular smooth muscle to regulate fluid and electrolyte metabolism [2]. In addition, ANP immunoreactivity and ANP receptors are present in mammalian brain [3,4]. In brain, ANP may act as a neuromodulator or neu- rotransmitter in the regulation of cardiovascular function and fluid balance [5 ]. Several lines of evidence suggest central actions of