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To define transmembrane and intracellular mechanisms of production and release of atrial natriuretic polypeptide (ANP) in the absence of mechanical atrial stretch, we studied the direct effects of physiological stimuli on isolated adult rat atrial myocytes maintained under tissue culture. Although stimulation of beta-adrenergic receptors on the surface of atrial myocytes by isoproterenol did not affect ANP release, adrenergic alpha-1 receptor stimulation by methoxamine enhanced ANP release with reciprocal intracellular ANP reduction. When muscarinic receptors were stimulated by acetylcholine, ANP release was accelerated and intracellular ANP reduced. The activation of the phosphatidylinositol system, which is a common pathway for muscarinic and alpha-1 adrenergic receptor stimulation, was thus considered to regulate ANP release, but not ANP production.

Biochemical mechanism of release of atrial natriuretic polypeptide.