In this twice revised new R29 application, Michael E. Bradley, Ph.D. requests $350,000 in direct costs over 5 years to study the """"""""molecular basis of nitric oxide action in primate myometrium."""""""" The long-term goal of this project is to understand the signals responsible for commencement of uterine contractions associated with labor.
The specific aim of this proposal is to determine if the tissues of the human or monkey uterus produce nitric oxide and whether nitric oxide can relax human or monkey uterine myocytes. The proposal is divided into 2 specific aims.
In specific aim 1 the investigator will determine the effects of exogenous NO in non-pregnant, near term pregnant, and laboring uterine tissues and cells. In this specific aim the investigator will determine the effects of NO on myometrial tissue tension and determine the effects on NO on the concentration of calcium, cAMP and cGMP.
In specific aim 2 the investigator will characterize, localize and investigate the regulation of NOS isoforms in the primate uterus. Techniques to be explored in this specific aim include Western blot analysis of intact tissues and cultured cells and determination of NOS mRNA expression using RT-PCR.
|Jiao, Xiuxiang; Gonzalez-Cabrera, Pedro J; Xiao, Lei et al. (2002) Tonic inhibitory role for cAMP in alpha(1a)-adrenergic receptor coupling to extracellular signal-regulated kinases 1/2. J Pharmacol Exp Ther 303:247-56|
|Bradley, K K; Bradley, M E (2001) Purine nucleoside-dependent inhibition of cellular proliferation in 1321N1 human astrocytoma cells. J Pharmacol Exp Ther 299:748-52|
|Thornburg, K L; Reller, M D (1999) Coronary flow regulation in the fetal sheep. Am J Physiol 277:R1249-60|
|Satterwhite, C M; Farrelly, A M; Bradley, M E (1999) Chemotactic, mitogenic, and angiogenic actions of UTP on vascular endothelial cells. Am J Physiol 276:H1091-7|
|Bradley, K K; Buxton, I L; Barber, J E et al. (1998) Nitric oxide relaxes human myometrium by a cGMP-independent mechanism. Am J Physiol 275:C1668-73|
|Kuenzli, K A; Buxton, I L; Bradley, M E (1998) Nitric oxide regulation of monkey myometrial contractility. Br J Pharmacol 124:63-8|