4-Aminopyridine activates an inhibitory alpha 1-adrenergic mechanism unmasked by nifedipin on the electrically stimulated rat vas deferens.
4-Aminopyridine (4-AP) acts by blocking voltage dependent potassium channels in excitable membrane thus increasing the influx of extracellular (Ca2+) in response to an action potential. 4-AP exerts either in vivo or in vitro effects in many organs. The present report deals with a study on the electrically stimulated rat vas deferens of the action of 4-AP on Ca2+ mediated mechanism related to the adrenergic transmission. To avoid the interference of the non-adrenergic components we used the epididymal portion of the vas. 4-AP was shown to enhance the electrically-stimulated contractions in a way which was inversely related to external Ca2+. This effect was abolished by nifedipine (1 x 10(-6) M). Unexpectedly, however, 4-AP acted synergistically with nifedipine by enhancing the inhibition of the electrically-induced tension sustained by nifedipine. This property of 4-AP was shared by noradrenaline, phenylephrine, clonidine, serotonin, morphine and ATP. Their inhibitory effects were antagonized by prazosin (1 x 10(-8) M), yohimbine (2.5 x 10(-5) M), methysergide (1 x 10(-4) M), naloxone (1.2 x 10(-7) M), and theophylline (6 x 10(-6) M) respectively. The inhibitory effect of 4-AP was antagonized only by prazosin (1 x 10(-8) M) and was not observed in vas deferens of rats pretreated with reserpine. It is concluded that 4-AP is able not only to activate excitatory mechanisms but also to stimulate inhibitory alpha 1-adrenergic mechanisms.
Mantovani
P
P
Institute of Pharmacological Sciences, School of Pharmacy, University of Siena, Italy.
Palmi
M
M
Petkov
V V
VV
Sgaragli
G P
GP
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004558:Electric Stimulation; D004822:Epididymis / Q000187:drug effects; D066298:In Vitro Techniques; D008297:Male; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009543:Nifedipine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects*; D014649:Vas Deferens / Q000187:drug effects
D015221:Potassium Channels; D011942:Receptors, Adrenergic, alpha; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D015761:4-Aminopyridine; D009543:Nifedipine; D002118:Calcium