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Am J Physiol Regul Integr Comp Physiol 282: R1739-R1745, 2002; doi:10.1152/ajpregu.00696.2001
0363-6119/02 $5.00
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Vol. 282, Issue 6, R1739-R1745, June 2002

Ribozyme compromise of adrenomedullin mRNA reveals a physiological role in the regulation of water intake

Meghan M. Taylor and Willis K. Samson

Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St. Louis, Missouri 63104

The adrenomedullin (AM) preprohormone is posttranslationally processed to result in two biologically active fragments, AM and proadrenomedullin NH2-terminal 20 peptide (PAMP). AM is thought to play a role in fluid and electrolyte balance by acting in brain to inhibit salt and water appetite and in the kidney to cause diuresis and natriuresis. We previously have shown that AM is necessary for the short-term regulation of salt intake. In this paper, we have designed a ribozyme, a catalytic RNA molecule, which specifically recognizes and cleaves the AM transcript. In cultured vascular smooth muscle cells, ribozyme treatment lowered AM mRNA and reduced peptide content. Intracerebroventricular administration of the ribozyme lowered hypothalamic AM content and led to an exaggerated drinking response in rats, demonstrating that endogenous, brain-derived AM is physiologically relevant and necessary for short-term control of water intake.

proadrenomedullin amino-terminal twenty peptide; fluid and electrolyte homeostasis; translation blockade


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