Abstract

The effects on guanylate cyclase and cyclic GMP accumulation of a synthetic peptide containing the amino acid sequence and biological activity of atrial natriuretic factor (ANF) were studied. ANF activated particulate guanylate cyclase in a concentration- and time- dependent fashion in crude membranes obtained from homogenates of rat kidney. Activation of particulate guanylate cyclase by ANF was also observed in particulate fractions from homogenates of rat aorta, testes, intestine, lung, and liver, but not from heart or brain. Soluble guanylate cyclase obtained from these tissues was not activated by ANF. Trypsin treatment of ANF prevented the activation of guanylate cyclase, while heat treatment had no effect. Accumulation of cyclic GMP in kidney minces and aorta was stimulated by ANF activation of guanylate cyclase. These data suggest a role for particulate guanylate cyclase in the molecular mechanisms underlying the physiological effects of ANF such as vascular relaxation, natriuresis, and diuresis.

Highlights

  • A peptide released from atria which stimulatessmooth the presence or absence of 3-isobutyl-1-methylxanthineand muscle relaxation and renal excretion of sodium and water M&B 22,948, a specific inhibitor of cyclic GMP phosphodihas recently been purified, sequenced, and characterized (1- esterase (14)

  • These results suggest that ANF activates par

  • Since guanylate cyclase and cyclic GMP have been demonstrated to play an integral role in the regulation of smooth muscle motility (4-8) and fluid and electrolyte balance (g-ll), we investigated the effects of a synthetic peptide containing the amino acid sequence of ANF 0 2 ) on guanylate cyclase in a variety of tissues from rat

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Summary

Cyclic GMP in Rat Tissues*

9, 11).High-speed (105,000 X g X 60 min) particulate and soluble fractions were obtained and used for determinations of guanylate (Received for publication, August 16, 1984). A peptide released from atria which stimulatessmooth the presence or absence of 3-isobutyl-1-methylxanthineand muscle relaxation and renal excretion of sodium and water M&B 22,948, a specific inhibitor of cyclic GMP phosphodihas recently been purified, sequenced, and characterized (1- esterase (14) These results suggest that ANF activates par-. Since guanylate cyclase and cyclic GMP have been demonstrated to play an integral role in the regulation of smooth muscle motility (4-8) and fluid and electrolyte balance (g-ll), we investigated the effects of a synthetic peptide containing the amino acid sequence of ANF 0 2 ) on guanylate cyclase in a variety of tissues from rat This peptide retains thenatriuretic and smooth muscle relaxant activity ascribed to native ANF (12, 13).

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Findings
This report demonstrates for the first time that an agent
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