Effects of 4-aminopyridine on the adrenergic nerve terminals of rabbit arteries.
Adrenergic nerves of the rabbit pulmonary artery and aorta were stimulated by electrical pulses (0.3 or 5 msec duration) and also by nicotine. The effects of 4-aminopyridine (4-AP), a potassium channel inhibitor, were investigated on contractile responses of these arteries or on 3H-efflux from [3H]norepinephrine-treated pulmonary artery in response to these stimuli. Tetrodotoxin (0.1-0.3 micro M) abolished the contractions and the 3H-efflux induced by an electrical pulse of 0.3 msec duration, but not the adrenergic responses induced by a pulse of 5 msec duration or by nicotine. The adrenergic responses to an electrical pulse of 5 msec (with tetrodotoxin) or nicotine were inhibited by guanethidine (10 micro M) or removal of the extracellular calcium. Thus, a short electrical pulse indirectly stimulates the adrenergic nerve terminals through conducted action potentials, whereas a long pulse or nicotine stimulates directly the terminals. 4-AP in concentrations over 10 micro M markedly augmented the adrenergic responses to these two electrical stimuli. The adrenergic response induced by nicotine was little affected by 4-AP in concentrations up to 100 micro M. At 300 micro M, 4-AP, the concentration-contraction curve of nicotine, shifted to the right and 3H-efflux was markedly reduced. This inhibitory effect of 4-AP on the contraction was not affected by alterations in the concentrations of extracellular calcium. 4-AP did not affect the responses to exogenously applied norepinephrine. These results indicate that 4-AP has inhibitory effects on nicotinic receptors of adrenergic nerve terminals and that nicotine releases norepinephrine in a manner which differs from the release seen with electrical stimulation.
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001158:Arteries / Q000187:drug effects* / Q000294:innervation; D004558:Electric Stimulation; D066298:In Vitro Techniques; D008297:Male; D009411:Nerve Endings / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism; D011817:Rabbits; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013779:Tetrodotoxin / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects
D000631:Aminopyridines; D013779:Tetrodotoxin; D009538:Nicotine; D015761:4-Aminopyridine; D009638:Norepinephrine