Dependence of release of [3H]noradrenaline from rabbit pulmonary artery on internal sodium.
1. [3H]Noradrenaline ([3H]NA) release from the isolated main pulmonary artery of the rabbit has been measured in the presence of uptake blockers (cocaine, 3 x 10(-5) M, and corticosterone, 5 x 10(-5) M) and after blocking the monoamine oxidase enzyme by pargyline (1.2 x 10(-4) M). 2. In normal Krebs solution Mn2+ (2 mM) significantly inhibited both [3H]NA release (approximately 80%; P < 0.001) and the contraction following 2 Hz field stimulation. 3. In Ca(2+)-free, EGTA (1 mM)-containing solution, the Na+ pump was inhibited by removal of K+ from the external medium. In Na+ pump-inhibited arteries, 2 mM Mn2+ (free Mn2+, 1 mM) increased the spontaneous release of [3H]NA according to the time of Na+ loading. TTX (10(-7) M) did not inhibit significantly the Mn(2+)-induced [3H]NA release from Na(+)-loaded preparations (percentage inhibition, approximately 24; P > 0.30). 4. Without Na+ loading (Ca2+ free, EGTA alone), Mn2+ failed to promote 3H release from arteries. 5. With constant Na+ loading (120 min 'K(+)-free' perfusion in Ca(2+)-free, 1 mM EGTA-containing solution), the release of 3H was also directly dependent on free Mn2+ concentration (0.2, 0.6 and 1 mM). 6. The Mn2+ (2 mM; free Mn2+, 1 mM)-induced 3H release from Na(+)-loaded nerves (120 min 'K(+)-free', perfusion) was further enhanced, when external Na+ was simultaneously reduced from 139.2 to 26.2 mM (choline+ or sucrose substitution). 7. Diphenylhydantoin (DPH, 10(-4) M) significantly reduced the Mn(2+)-evoked 3H release (approximately 44%; P < 0.02) when it was present during 'K(+)-free', perfusion. 8. Mn2+ was ineffective in releasing 3H if the Na+ pump was previously reactivated by readmission of K+ to Na(+)-loaded arteries. 9. It is concluded that in Ca(2+)-free solution Mn2+ releases neurotransmitter in a manner which depends on the degree of loading with internal Na+. The results suggest this depends at least partly on a block of Ca2+ efflux.
Török
T L
TL
Department of Pharmacodynamics, Semmelweis University of Medicine, Budapest, Hungary.
Tóth
P T
PT
Tóthfalusi
L
L
Azzidani
A M
AM
Magyar
K
K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D066298:In Vitro Techniques; D008297:Male; D008345:Manganese / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000294:innervation*; D009638:Norepinephrine / Q000378:metabolism*; D010672:Phenytoin / Q000494:pharmacology; D011651:Pulmonary Artery / Q000294:innervation; D011817:Rabbits; D012964:Sodium / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects; D013779:Tetrodotoxin / Q000494:pharmacology
D008345:Manganese; D013779:Tetrodotoxin; D010672:Phenytoin; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D009638:Norepinephrine