[Pre- and postsynaptic action of the ATP-dependent K+-channel-(K+ATP)-opener pinacidil in rabbit pulmonary artery].
Low frequency (2 Hz) of electrical depolarisation induced [3H]noradrenaline ([3H]NA) release has been measured from the isolated main pulmonary artery of the rabbit in the presence of uptake blockers (cocaine, 3x10(-5)M and corticosterone, 5x10(-5)M), with parallel measurements of post-junctional contractile responses. The K+ATP-channel opener pinacidil (10(-6)-10(-4)M), slightly potentiated the nerve-evoked release of [3H]NA which failed to show close concentration-dependency. Large concentration of pinacidil (10(-4)M) increased the ratio of [3H]NA release from 0.99 +/- 0.02 to 1.28 +/- 0.05 (P < 0.0005). On the other hand, pinacidil inhibited the nerve-evoked contractions in a concentration-dependent manner. 10(-4)M caused nearly 70% inhibition of contractile response. The pre- and post-junctional effects of pinacidil were studied under the following experimental conditions: 1) exogenously applied 1-NA; 2) excess K+; 3) 'L-type' Ca(2+)-channel activation (BAY K 8644); K(+)-channel inhibition (4-AP); and 5) Na(+)-pump inhibition/reactivation. Pinacidil (10(-4)M) retained its marginal NA-release stimulatory effect in all cases. However, pinacidil inhibited the contraction of smooth muscle, although to a different extent, in all of the experimental conditions used in our study.
Semmelweis Orvostudományi Egyetem Gyógyszerhatástani Intézete, Budapest.
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Rácz
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Zillikens
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Forstreuter
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Magyar
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Török
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D003345:Corticosterone / Q000494:pharmacology; D004558:Electric Stimulation; D015640:Ion Channel Gating / Q000187:drug effects / Q000502:physiology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism; D020110:Pinacidil / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology*; D017729:Presynaptic Terminals / Q000187:drug effects / Q000502:physiology; D011651:Pulmonary Artery / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D011817:Rabbits; D013569:Synapses / Q000187:drug effects / Q000502:physiology*
D015221:Potassium Channels; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D020110:Pinacidil; D000255:Adenosine Triphosphate; D003345:Corticosterone; D009638:Norepinephrine
Az ATP-függó K(+)-csatorna-(K+ATP)-aktiváló pinacidil pre- és poszt-szinaptikus hatása nyúl pulmonáris artérián.