Postjunctional effect of pinacidil on contractility of isolated bovine trachealis.
Potassium channel openers hyperpolarize the smooth muscle cell membrane and relax airway smooth muscle. In this study, pre- and postjunctional effects of pinacidil ((+/-) N-cyano-N'-(4-pyridil)-N"-(1,2,2-trimethylpropyl)-guanidine monohydrated), an adenosine triphosphate (ATP)-sensitive K(+)-channel opener, were determined in isolated bovine trachealis. The effects of pinacidil on the frequency-response to electrical field stimulation (EFS), 0.1-32 Hz, and on the concentration response to acetylcholine (ACh), 10(9)-10(-4) M, were compared in muscle strips from six animals. In addition, the effect of pinacidil on the inhibitory nonadrenergic noncholinergic (iNANC) system was evaluated in histamine-contracted muscle strips from another eight animals. Pinacidil (10(-6) or 10(-5) M) shifted both the EFS frequency-response and the ACh concentration-response curves significantly (p < 0.01) to the right. Glibenclamide (10(-7)-10(-5) M) antagonized these responses in a concentration-dependent manner. The inhibitory effects of pinacidil on contractions of the same magnitude induced by EFS or exogenous ACh were not significantly different (p = 0.11), suggesting that pinacidil had only a postjunctional effect. Pinacidil had no effect on iNANC-mediated muscle relaxation. We conclude that pinacidil attenuates the contraction of isolated bovine tracheal smooth muscle by postjunctional mechanisms.
Cattedra di Fisiopatologia Respiratoria, DISM, Facoltà di Medicina e Chirurgia, Università di Genova, Italy.
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Song
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Rocchi
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Lazzarotti
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Crimi
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Rehder
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Brusasco
D000109:Acetylcholine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D002417:Cattle; D002462:Cell Membrane / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005905:Glyburide / Q000008:administration & dosage / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology*; D006632:Histamine / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects*; D009126:Muscle Relaxation / Q000187:drug effects; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects* / Q000294:innervation; D020110:Pinacidil; D015221:Potassium Channels / Q000187:drug effects*; D017981:Receptors, Neurotransmitter / Q000187:drug effects; D013237:Stereoisomerism; D014132:Trachea / Q000166:cytology / Q000187:drug effects*
D006146:Guanidines; D015221:Potassium Channels; D017981:Receptors, Neurotransmitter; D020110:Pinacidil; D006632:Histamine; D000109:Acetylcholine; D005905:Glyburide