Relaxant effects of parathyroid hormone and parathyroid hormone-related peptides on oviduct motility in birds and mammals: possible role of nitric oxide

Abstract

Parathyroid hormone (PTH) and PTH-related peptides (PTHrP) have previously been shown to modulate the contractile state of numerous types of smooth muscle. The effects of N-terminal PTH and PTHrP on spontaneous in vitro contractility of oviducal smooth muscle using tissues from egg-laying Japanese quail (10-15 h post ovulation), 4 and 9 days pregnant mouse uterus were investigated. Myometrial tissues from both species contracted vigorously for several hours, when incubated in organ baths in De Jalon's solution gassed with 5%CO2/95%O2. Contractions were enhanced in high (1.2-2.5 mM) compared with low (0.1-0.5 mM) calcium (Ca) containing media. Bovine PTH(1-34) (bPTH(1-34)), human PTH(1-34 amide) (hPTHrP(1-34) amide), and hPTHrP(1-40) caused similar concentration-related inhibition of contractions in media containing 1.2mM Ca over a range of 10(-9) to 10(-7)M, whereas C-terminal hPTHrP(107-139) was devoid of such activity. Responses to bPTH(1-34) in 4 and 9-day pregnant mouse tissues were similar but hPTHrP(1-40) showed substantial loss of activity in 9-day, compared with 4-day pregnant mouse tissues. Repeated exposure of mouse uterine tissue to the peptides resulted in desensitisation of responses. The EC50 responses of mouse tissues were inhibited by the PTH/PTHrP receptor antagonist, hPTHrP(7-34) amide. Responses to bPTH(1-34) were also inhibited by both non-selective and selective neuronal nitric oxide synthase (NOS) inhibitors N(omega)-nitro-L-arginine methyl ester (0.01-1mM) and 7-nitroindazole (0.01-10 microM), respectively. Both NOS inhibitors were more effective in inhibiting bPTH(1-34)-induced relaxation in the absence of L-arginine compared with in the presence of 1mM L-arginine (a NOS substrate) in the incubation media. It is concluded that relaxant responses to N-terminal PTH and PTHrP peptides are well conserved in oviducal and uterine tissues from avian and mammalian species. The results also suggest that NO may be responsible for mediating relaxant activities of these peptides in pregnant mouse uterine tissue.