Atrial natriuritic factor (ANF) and brain natriuritic peptide (BNP) are structurally related cardiac-derived peptides with a vasorelaxant diurtic and natriuretic activities that oppose the action of substances responsible for increasing volume and blood pressure. While the ANF and BNP genes are co-induced by pressor substances, BNP is induced surprisingly quickly as an immediate early or primary response gene (PRG) while ANF is induced slowly as a late or secondary response gene (SRG). The differential induction of BNP and ANF implies that the peptides may serve distinct physiological roles. The proposal focuses on studies of the molecular mechanisms responsible for the complex induction of BNP and ANP by alpha 1 adrenergic agonists. The hypothesis is that while both genes are transcriptionally induced, stabilization of the normally labile BNP mRNA constitutes an important feature of its induction.
The specific aims are: (1) to study the 5' cis elements that confer alpha 1 adrenergic agonists inducible transcription, (2) to characterize proteins and interact with these cis-elements and to determine how they mediate inducible transcription, (3) to identify elements in ANF and BNP mRNA that influence transcript half-life and (4) to determine how the cis-regulatory elements contribute to ANF and BNP induction in the intact rat myocardium. These studies will lead not only to a better understanding of the hemodynamic role of ANF and BNP but will also provide new information relating to cardiac specific and hormone inducible gene expression.
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