Endocrine Abstracts (2002) 3 P211

Parathyroid polyhormone action on motility of pregnant mouse uterus in vitro: Role of nitric oxide

M Francis, S Precious, J Brown & CG Dacke

School of Pharmacy and Biomedical Sciences, University of Portsmouth, UK.

The effects of N-terminal parathyroid hormone (PTH) and parathyroid hormone related peptides (PTHrP) on the spontaneous contractility of 4 days pregnant mouse uterus in vitro were investigated. The myometrial tissue contracted vigorously for several hours, when incubated in organ baths in De Jalon's solution. PTH(1-34) and PTHrP(1-40) caused similar dose related inhibitions of contractions over a dose range of 10-9 to 10-7 M. C terminal PTHrP(107-139) was devoid of this activity. Repeated dosing with the peptides produced tachyphylaxis. The EC50 responses were partially inhibited by a PTH/PTHrP receptor antagonist, PTHrP(7-34) amide. The responses were inhibited by nitric oxide synthase inhibitors N-omega-nitro-L-arginine methyl ester (0.01-1mM) and 7-nitroindazole(0.01-10 micro M). These results suggest the possible role of NO in mediating the relaxant activity of parathyroid polyhormones. Identification of the cells responsible for NO production in response to PTH was achieved by loading cryostat cut sections (10 micro M) of pregnant mouse uterus with a NO sensitive fluorescent dye 4,5-diaminofluorescein (DAF-2; 10 micro M). NO producing cells appeared to be evenly distributed throughout the myometrium suggesting that NO may be produced in neuronal cells. It is concluded that PTH peptides may play a regulatory role in controlling endometrial contractility during pregnancy and parturition and that NO is involved in mediating this process.

Article tools

My recent searches

No recent searches.