tailieunhanh - Báo cáo khoa học: cGMP-dependent protein kinase II and aldosterone secretion

Oligomeric assemblies of amyloid-b(Ab) are suggested to be central in the pathogenesis of Alzheimer’s disease because levels of soluble Abcorrelate much better with the extent of cognitive dysfunctions than do senile plaque counts. Moreover, such Abspecies have been shown to be neurotoxic, to interfere with learned behavior and to inhibit the maintenance of hippo-campal long-term potentiation. | ỊFEBS Journal cGMP-dependent protein kinase II and aldosterone secretion Beate SpieBberger1 Dominik Bernhard1 Stefan Herrmann1 Susanne Feil1 f Claudia Werner1 Ị Peter B. Luppa2 and Franz Hofmann1 1 Institut fur Pharmakologie und Toxikologie Medizinische Fakultat Technische Universitat Munchen Germany 2 Institut fur Klinische Chemie und Pathobiochemie Medizinische Fakultat Technische Universitat Munchen Germany Keywords ACTH ANP adrenal gland blood pressure cGMP Correspondence F. Hofmann Institut fur Pharmakologie und Toxikologie Technische Universitat Munchen Biedersteiner StraBe 29 80802 Munchen Germany Fax 49 89 4140 32450 Tel 49 89 4140 3241 E-mail hofmann@ These authors contributed equally to this paper Present address flnterfakultares Institut fcur Biochemie Univ Tubingen Germany tDipartimento di Farmacologia Preclinica e Clinica Firenze Italy Received 7 August 2008 revised 3 December 2008 accepted 5 December 2008 doi ACTH-stimulated aldosterone secretion can be inhibited by atrio-natri-uretic peptide cGMP. The mechanism behind this modulation has been reported to involve cGMP-dependent activation of phosphodiesterase 2 PDE2 and hydrolysis of cAMP. Recently it was reported that activation of cGMP-dependent protein kinase II cGKII stimulated aldosterone secretion in rat zona glomerulosa cells. The zona glomerulosa of the murine adrenal cortex expresses cGKII and PDE2. We used mice with a homozygous inactivation of the cGKII gene to investigate in vivo the potential role of this kinase in aldosterone secretion. Basal plasma renin and aldosterone levels were similar in wild-type and cGKII _ mice. In vivo injection of atrio-natriuretic peptide decreased ACTH-stimulated aldosterone secretion in wild-type mice but had no effect in cGKII-deficient mice. These results support the view that cGKII modulates aldosterone secretion in the murine adrenal cortex. The major physiological function of the glomerulosa layer of the .