Effects of potassium channel inhibitors on nitrergic and adrenergic neurotransmission in lamina propria of the female rabbit urethra.
Electrical field stimulation of strip preparations of the female rabbit urethral lamina propria induces a frequency-dependent adrenergic contraction or a non-adrenergic, non-cholinergic (NANC) relaxation, mediated by nitric oxide, depending on the prevailing tension. To study the role of potassium channels in these responses, the effects of inhibitors of voltage-dependent (dendrotoxin I, 4-aminopyridine), low (apamin) and high (iberiotoxin, charybdotoxin) conductance calcium-activated and ATP-sensitive (glibenclamide) potassium channels on the frequency-response relationship were examined. 4-Aminopyridine (1 mM), but none of the other inhibitors, augmented the NANC relaxation. The maximal response was, however, unaffected by 4-aminopyridine. The adrenergic contraction was enhanced by 4-aminopyridine (1 mM), dendrotoxin I (0.1 microM), iberiotoxin (0.1 microM) and charybdotoxin (0.1 microM), but not by apamin (0.1 microM) and glibenclamide (10 microM). Besides reducing the frequency eliciting half maximal contraction dendrotoxin and charybdotoxin also enhanced the maximal response. None of the inhibitors affected the relaxation induced by the nitric oxide donor 3-morpholinosydnonimine or the contraction elicited by noradrenaline. The results suggest that dendrotoxin-sensitive voltage-dependent and high conductance calcium-activated neuronal potassium channels participate in adrenergic, but not in nitrergic, neurotransmission in the lamina propria of the female rabbit urethra. This offers a possibility to selectively interfere with the adrenergic neuroeffector system with drugs acting on these K-channels.
Zygmunt
P K
PK
Department of Clinical Pharmacology, Lund University Hospital, Sweden.
Högestätt
E D
ED
Andersson
K E
KE
D015761:4-Aminopyridine / Q000494:pharmacology; D000320:Adrenergic Fibers / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002799:Cholinergic Fibers / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007004:Hypoglycemic Agents / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009126:Muscle Relaxation / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011817:Rabbits; D009435:Synaptic Transmission / Q000187:drug effects*; D014521:Urethra / Q000187:drug effects* / Q000502:physiology
D007004:Hypoglycemic Agents; D010455:Peptides; D026902:Potassium Channel Blockers; D001030:Apamin; C064719:iberiotoxin; D015761:4-Aminopyridine; D005905:Glyburide