RELAXATION OF PORCINE TRACHEAL SMOOTH-MUSCLE BY PARATHYROID HORMONE-RELATED PROTEIN

Parathyroid hormone-related protein (PTHrp) has been shown to relax ut erine and gastrointestinal smooth muscles, but the mechanisms underlyi ng its effects have not been characterized. Furthermore, its effect on pulmonary smooth muscle is unknown. Therefore we designed the present study to determine the PTHrp dose-response; the interaction of PTHrp and PTH; and the role of cyclic nucleotides and potassium channels in the PTHrp response in porcine tracheal smooth muscle (TSM). Our result s indicate that, (1-34)PTHrp causes dose-dependent relaxation of TSM; that (1-34)PTHrp and (1-34)PTH demonstrate cross-tachyphylaxis to one another; that phosphodiesterase inhibition augments and phosphodiester ase stimulation attenuates the relaxation response while guanylate cyc lase blockade has little effect, and that charybdotoxin and iberiotoxi n, inhibitors of large conductance, Ca2+-activated, K+ channels, dimin ish the relaxation response. These findings suggest that (1-34)PTHrp-i nduced relaxation of TSM is mediated through a common PTHrp/PTH pathwa y or receptor, stimulation of cAMP and activation of large conductance , Ca2+-activated, K+ channels. (C) 1997 Elsevier Science B.V.