title: Prejunctional actions of K+ channel blockers in rat vas deferens.
abstract: In studies of isometric contractions in prostatic portions of rat vas deferens evoked by single pulse electrical stimulation, the K+ channel blockers 4-aminopyridine, tetraethylammonium and charybdotoxin, but not apamin, significantly reduced the prejunctional inhibitory potency and the maximum inhibitory effect of the alpha 2-adrenoceptor agonist xylazine. The protein kinase C activator phorbol dibutyrate had similar effects to 4-aminopyridine against xylazine. However, 4-aminopyridine, tetraethylammonium, charybdotoxin and phorbol dibutyrate, but not apamin, significantly increased the magnitude of the isometric contraction to a single stimulus. 4-Aminopyridine and phorbol dibutyrate significantly reduced, while tetraethylammonium did not affect, isometric contractions to noradrenaline, and 4-aminopyridine failed to affect contractions to alpha,beta-methylene-ATP, so that the effects of these agents on the isometric contraction to a single stimulus were presumably by a prejunctional action. The Ca2+ entry facilitator Bay K 8644 (1,4-dihydro-2,6-dimethyl-5-nitro-4-[2-(trifluoromethyl)-phenyl]-3-pyrid ine carboxylic acid methylester) increased stimulation-evoked contractions by a postjunctional action and reduced the inhibitory effects of xylazine. When the isometric contraction following 4-aminopyridine was reduced by decreasing the stimulation voltage or by reducing the Ca2+ concentration from 2.5 to 0.9 mM, 4-aminopyridine significantly reduced the potency of xylazine. However, tetraethylammonium and Bay K 8644 failed to affect the inhibitory potency of xylazine in low Ca2+. It is concluded that the K+ channel blocker 4-aminopyridine reduces the prejunctional inhibitory potency of xylazine, and this action is independent of increased neurotransmitter release. These results suggest that prejunctional alpha 2-adrenoceptor-mediated inhibition in rat vas deferens involves K+ channels sensitive to block by 4-aminopyridine.
authors.affiliation: Department of Physiology, Royal College of Surgeons in Ireland, Dublin.
authors.forename: J R
authors.initials: JR
authors.lastname: Docherty
authors.forename: G
authors.initials: G
authors.lastname: Brady
mesh_terms: 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; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000777:Anesthetics / Q000494:pharmacology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D018999:Charybdotoxin / Q000494:pharmacology; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009469:Neuromuscular Junction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects*; D013329:Structure-Activity Relationship; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism; D014991:Xylazine / Q000494:pharmacology
chemical_list: D000777:Anesthetics; D026902:Potassium Channel Blockers; D018341:Receptors, Adrenergic, alpha-2; D013757:Tetraethylammonium Compounds; D018999:Charybdotoxin; D001030:Apamin; D014991:Xylazine; D015240:Phorbol 12,13-Dibutyrate; D019789:Tetraethylammonium; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000255:Adenosine Triphosphate; D015761:4-Aminopyridine; D011493:Protein Kinase C; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; D002118:Calcium; D009638:Norepinephrine