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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD022063-04
Application #
3321364
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1987-06-01
Project End
1990-05-31
Budget Start
1989-06-01
Budget End
1990-05-31
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
University of Chicago
Department
Type
Schools of Medicine
DUNS #
225410919
City
Chicago
State
IL
Country
United States
Zip Code
60637
Bieber, E; Stratman, T; Sanseverino, M et al. (1998) Phosphatidylinositol-specific phospholipase C isoform expression in pregnant and nonpregnant rat myometrial tissue. Am J Obstet Gynecol 178:848-54
Phillippe, M; Saunders, T; Basa, A (1997) Intracellular mechanisms underlying prostaglandin F2alpha-stimulated phasic myometrial contractions. Am J Physiol 273:E665-73
Phillippe, M; Basa, A (1997) Effects of sodium and calcium channel blockade on cytosolic calcium oscillations and phasic contractions of myometrial tissue. J Soc Gynecol Investig 4:72-7
Harris, C M; Saunders, T; Baunoch, D A et al. (1997) Gq-protein alpha subunit expression and distribution in pregnant rat myometrial tissues. J Soc Gynecol Investig 4:209-17
Principe, D; Sanseverino, M; Saunders, T et al. (1997) Beta-adrenergic receptor subtype gene expression in timed-pregnant rat myometrium. Am J Obstet Gynecol 176:349-57
Chien, E K; Tokuyama, Y; Rouard, M et al. (1997) Identification of gestationally regulated genes in rat myometrium by use of messenger ribonucleic acid differential display. Am J Obstet Gynecol 177:645-52
Chien, E K; Saunders, T; Phillippe, M (1996) The mechanisms underlying Bay K 8644-stimulated phasic myometrial contractions. J Soc Gynecol Investig 3:106-12
Phillippe, M; Chien, E M; Freij, M et al. (1995) Ionomycin-stimulated phasic myometrial contractions. Am J Physiol 269:E779-85
Phillippe, M (1995) The effects of thimerosal, a sulfhydryl reagent, on phasic myometrial contractions. Biochem Biophys Res Commun 211:1-6
Phillippe, M; Chien, E K (1995) Potassium chloride effects on the hormonal signal transduction mechanisms underlying phasic myometrial contractions. J Endocrinol 146:485-93

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