Potassium channel inhibitors attenuate neuromodulatory effects of atrial natriuretic factor in the rabbit isolated vas deferens.
This study tested the hypothesis that neuromodulatory effects of atrial natriuretic factor (ANF) are mediated by an activation of potassium channels in the rabbit isolated vas deferens. The neuromodulatory effects of ANF were tested in the presence of the potassium channel inhibitors, tetraethylammonium, 4-aminopyridine, glibenclamide and charybdotoxin. The effects of the first three were ascertained by their prevention of neuromodulatory effects of a cromokalim enantiomer (BRL 38227), which opens ATP-sensitive potassium channels. The nonspecific potassium channel inhibitors, tetraethylammonium (2 mM) and 4-aminopyridine (2 mM) blocked inhibitory effects of both ANF and BRL 38227 on the electrically-induced adrenergic contraction in the rabbit vas deferens. Glibenclamide (10 microM), an inhibitor of ATP-sensitive potassium channels, failed to antagonize ANF effects, but blocked the actions of BRL 38227. Charybdotoxin (100 nM) is known to block large conductance calcium-activated potassium channels, and it attenuated the neuromodulatory effects of ANF; however, the effects of BRL 38227 were sustained in the presence of charybdotoxin. These results are consistent with the hypothesis that the neuromodulatory action of ANF is mediated by the activation of potassium conductances. The potassium channel involved is not an ATP-sensitive channel, because glibenclamide failed to alter the neuromodulatory activity of ANF. We hypothesize that ANF effects could be mediated by an activation of either calcium-activated or outward rectifying potassium channels.
Kanwal
S
S
Department of Pharmacology, School of Medicine, University of Minnesota-Duluth.
Trachte
G J
GJ
D015761:4-Aminopyridine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000494:pharmacology*; D001578:Benzopyrans / Q000494:pharmacology; D018999:Charybdotoxin; D019806:Cromakalim; D005905:Glyburide / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009638:Norepinephrine / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects; D011224:Prazosin / Q000494:pharmacology; D011758:Pyrroles / Q000494:pharmacology; D011817:Rabbits; D011941:Receptors, Adrenergic / Q000187:drug effects; D012604:Scorpion Venoms / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000294:innervation
D001578:Benzopyrans; D026902:Potassium Channel Blockers; D015221:Potassium Channels; D011758:Pyrroles; D011941:Receptors, Adrenergic; D012604:Scorpion Venoms; D013757:Tetraethylammonium Compounds; D019806:Cromakalim; D018999:Charybdotoxin; D019789:Tetraethylammonium; D009320:Atrial Natriuretic Factor; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D005905:Glyburide; D009638:Norepinephrine; D011224:Prazosin