Relaxation of porcine tracheal smooth muscle by parathyroid hormone-related protein.
Parathyroid hormone-related protein (PTHrp) has been shown to relax uterine and gastrointestinal smooth muscles, but the mechanisms underlying 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 results 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 phosphodiesterase stimulation attenuates the relaxation response while guanylate cyclase blockade has little effect, and that charybdotoxin and iberiotoxin, inhibitors of large conductance, Ca(2+)-activated, K+ channels, diminish the relaxation response. These findings suggest that (1-34)PTHrp-induced relaxation of TSM is mediated through a common PTHrp/PTH pathway or receptor, stimulation of cAMP and activation of large conductance, Ca(2+)-activated, K+ channels.
Shenberger
J S
JS
Department of Pediatrics/PSP, Wilford Hall USAF Medical Center, Lackland AFB, TX 78236-5300, USA.
Shew
R L
RL
Johnson
D E
DE
Kannan
M S
MS
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D010277:Parasympathomimetics / Q000494:pharmacology; D010281:Parathyroid Hormone / Q000494:pharmacology*; D044162:Parathyroid Hormone-Related Protein; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated; D011506:Proteins / Q000008:administration & dosage / Q000494:pharmacology*; D018016:Receptors, Parathyroid Hormone / Q000378:metabolism; D013552:Swine; D014132:Trachea / Q000187:drug effects
D000634:Aminoquinolines; D004791:Enzyme Inhibitors; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010277:Parasympathomimetics; D010281:Parathyroid Hormone; D044162:Parathyroid Hormone-Related Protein; D010726:Phosphodiesterase Inhibitors; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D011506:Proteins; D018016:Receptors, Parathyroid Hormone; D002217:Carbachol; C041715:6-anilino-5,8-quinolinedione; D000242:Cyclic AMP; D015056:1-Methyl-3-isobutylxanthine