The specific aim is to begin to characterize the biochemistry and physiology of uterine myocyte adrenoceptors (i.e. alpha-1, alpha-2, and beta-2 adrenergic receptors). Adrenergic agonists have previously been reported to play a significant role in the contractile activity of uterine smooth muscle. Recently reported studies utilizing non-uterine tissues, including other types of smooth muscle, have described the biochemical mechanisms of transmembrane transmission of adrenergic stimulation of all three of these receptors: beta stimulation increases intracellular c-AMP, alpha-1 stimulation results in hydrolysis of polyphosphoinositides, and alpha-2 stimulation inhibits adenylate cyclase activity. The properties of these receptors will be identified utilizing a series of experiments including: a) characterization of these adrenergic receptors in cultured rabbit uterine myocytes, b) characterization of these receptors in cultured uterine myocytes after steroid (estradiol, progesterone, and cortisol) exposure, c) description of the biochemical events occuring with transmembrane signal transmission, and subsequent intracellular second messengers produced by these receptors in cultured uterine myocytes, and d) utilization of in vitro isometric contraction studies to establish the physiologic significance of each of these adrenergic receptors. Disturbances of parturition, especially premature labor, are the most important clinical events related to perinatal mortality in the United States. At the present time pharmacologic stimulation of the beta adrenergic receptor is one of the most effective methods of arresting premature labor, thereby preventing prematurity with all of its associated morbidity and mortality risks. Similarly, the ability of ergot alkaloids to stimulate the myometrial alpha adrenergic receptors has provided the clinician with a very important pharmacologic tool for the treatment of postpartum uterine atony. Clarification of the biochemistry and physiology of uterine myocyte adrenoceptors will ultimately improve the understanding of uterine contractile activity, including events related to parturition.
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