Skip to main content
Log in

Effects of potassium channel inhibitors on nitrergic and adrenergic neurotransmission in lamina propria of the female rabbit urethra

  • Original Articles
  • Published:
Naunyn-Schmiedeberg's Archives of Pharmacology Aims and scope Submit manuscript

Abstract

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 μM), iberiotoxin (0.1 μM) and charybdotoxin (0.1 μM), but not by apamin (0.1 μM) and glibenclamide (10 μM). 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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Berkow SG (1953) The corpus spongeosum of the urethra: its possible role in urinary control and stress incontinence in women. Am J Obstet Gynecol 65:346–351

    Google Scholar 

  • Dawson TM, Bredt DS, Fotuhi M, Hwang PM, Snyder SH (1991). Nitric oxide synthase and neuronal NADPH diaphorase are identical in brain and peripheral tissues. Proc Natl Acad Sci USA 88:7797–7801

    Google Scholar 

  • Chandy KG, Gutman GA (1995) Voltage-gated potassium channel genes. In:North RA (ed) Handbook of receptors and channels, ligand and voltage-gated ion channels. CRC Press, Boca Raton 1–71

    Google Scholar 

  • De Man JG, Boeckxstaens GE, Pelckmans PP, De Winter BY, Herman AG, Van Maercke YM (1993) Prejunctional modulation of the nitrergic innervation of the canine ileocolonic junction via potassium channels. Br J Pharmacol 110:559–564

    Google Scholar 

  • Edwards G, Weston AH (1994) Effect of potassium channel modulating drugs on isolated smooth muscle. In: Szekeres L, Papp GJ (eds) Handbook of experimental pharmacology, III. Springer, Berlin Heidelberg New York, pp. 469–531

    Google Scholar 

  • Ellis JL, Conanan ND (1994) Effects of potassium channel blockers on relaxation to a nitric oxide donor and to nonadrenergic nerve stimulation in guinea pig trachea. J Pharmacol Exp Ther 271:782–786

    Google Scholar 

  • Galvan M (1992) Potassium channels in mammalian neurones: their properties and prospects for pharmacological manipulation. In: Weston AH, Hamilton TC (eds) Potassium channel modulators. Blackwell, Oxford, pp 204–236

    Google Scholar 

  • Garcia ML, Galverez A, Garcia-Calvo M, King VF, Vazquez J, Kaczorowski GJ (1991) Use of toxins to study potassium channels, J Bioenerg Biomembr 23:615–646

    Google Scholar 

  • Garcia ML, Knaus H-G, Munujos P, Slaughter RS, Kaczorowski GJ (1995) Charybdotoxin and its effects on potassium channels. Am J Physiol 269:01–010

    Google Scholar 

  • Grissmer S, Nguyen An, Aiyar J. Hanson DC, Mather RJ, Gutman GA, Karmilowicz MJ, Auperin DD, Chandy KG (1994) Pharmacological characterization of five cloned voltage-gated K+ channels, types Kv 1.1, 1.2, 1.3, 1.5, and 3.1, stably expressed in mammalian cell lines. Mol Pharmacol 45:1227–1234

    Google Scholar 

  • Hall A, Stow J, Sorensen R, Dolly JO, Owen D (1994) Blockade by dendrotoxin homologues of voltage-dependent K+ currents in cultured sensory neurones from neonatal rats. Br J Pharmacol 113:959–967

    Google Scholar 

  • Hope BT, Michael GJ, Knigge KM, Vincent SR (1991) Neuronal NADPH diaphorase is a nitric oxide synthase. Proc Natl Acad Sci USA 88:2811–2814

    Google Scholar 

  • Hopkins WF, Allen ML, Houamed KM, Tempel BI (1994) Properties of voltage-gated K+ currents expressed in Xenopus oocytes by mKvl.l., mKv1.2 and their heteromultimers as revealed by mutagenesis of dendrotoxin-binding site in mKv1.1. Pflügers Arch 428:382–390

    Google Scholar 

  • Mattiasson A, Andersson K-E, Sjögren C (1985) Contractant and relaxant properties of the female rabbit urethral submucosa. J Urol 133:304–310

    Google Scholar 

  • Persson K, Alm P, Johansson K, Larsson B, Andersson K-E (1993) Nitric oxide synthase in pig lower urinary tract: immunohistochemistry, NADPH diaphorase histochemistry and functional effects. Br J Pharmacol 110:521–530

    Google Scholar 

  • Rud T, Andersson K-E, Asmussen M, Hunting A, Ulmsten U (1980) Factors maintaining the intraurethral pressure in women. Invest Urol 17:343–347

    Google Scholar 

  • Schweitz H, Bidard J-N, Maes P. Lazdunski M (1989a) Charybdotoxin is a new member of the K+ channel family that includes dendrotoxin I and mast cell degranulating peptide. Biochemistry 28:9708–9714

    Google Scholar 

  • Schweitz H, Stansfeld CE, Bidard J-N, Farni L, Maes P, Lazdunski M (1989b) Charybodotoxin blocks dendrotoxin-sensitive voltage-activated K+ channels. FEBS Lett 250:519–522

    Google Scholar 

  • Zygmunt PKE, Persson K, Alm P, Larsson B, Andersson K-E (1993) The L-arginine/nitric oxide pathway in the rabbit urethral lamina propria. Acta Physiol Scand 148:431–439

    Google Scholar 

  • Zygmunt PKE, Zygmunt PM, Högestätt EF, Andersson K-E (1995) NANC neurotransmission in lamina propria of the rabbit urethra: regulation by different subsets of calcium channels. Br J Pharmacol 115:1020–1026

    Google Scholar 

  • Zygmunt PM, Zygmunt PKE, Högestätt ED, Andersson K-E (1993) Effects of ω-conotoxin on adrenergic, cholinergic and NANC neurotransmission in the rabbit urethra and detrusor. Br J Pharmacol 110:1285–1290

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Zygmunt, P.K.E., Högestätt, E.D. & Andersson, KE. Effects of potassium channel inhibitors on nitrergic and adrenergic neurotransmission in lamina propria of the female rabbit urethra. Naunyn-Schmiedeberg's Arch Pharmacol 354, 336–342 (1996). https://doi.org/10.1007/BF00171065

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00171065

Key words

Navigation