Study of the mechanism of the relaxant action of (+)-glaucine in rat vas deferens

Br J Pharmacol. 1993 Nov;110(3):943-8. doi: 10.1111/j.1476-5381.1993.tb13904.x.

Abstract

1. Effects of the aporphinoid alkaloid, (+)-glaucine, on rat vas deferens were investigated. 2. (+)-Glaucine (2-18 microM) competitively inhibited contractions induced by noradrenaline and methoxamine with a pA2 value of about 6. 3. (+)-Glaucine (2 and 18 microM) did not change the accumulation of tritium during incubation of the vas deferens with [3H]-noradrenaline. 4. (+)-Glaucine (0.3 nM-0.1 mM) inhibited specific [3H]-prazosin binding to membranes from rat vas deferens with a pKi value of 6.63, which is close to the pA2 value obtained against noradrenaline and methoxamine in functional studies. 5. In electrically-stimulated rat vas deferens, (+)-glaucine (0.3-10 microM) enhanced twitch contractions and competitively antagonized the inhibitory effect of clonidine with a pA2 value of 5.91. 6. In tissues incubated in depolarizing calcium-free high-potassium medium, (+)-glaucine (30-80 microM) inhibited Ca(2+)-induced contractions with depression of the maximal response at higher doses and with a pD'2 value of 3.65. Furthermore, (+)-glaucine (50 microM) did not modify basal 45Ca uptake but strongly inhibited the influx of 45Ca induced by K+. 7. These results suggest that (+)-glaucine has non-selective alpha 1- and alpha 2-adrenoceptor blocking properties. At higher doses, (+)-glaucine shows calcium antagonist activity which may be responsible, at least in part, for the inhibition of the contractions induced by Ca2+ in calcium-free high-potassium medium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antitussive Agents / pharmacology*
  • Aporphines / pharmacology*
  • Calcium / metabolism
  • Calcium / pharmacokinetics
  • Calcium Chloride / pharmacology
  • Calcium Radioisotopes
  • Cell Membrane / metabolism
  • Electric Stimulation
  • Hydroxylamines / pharmacology
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle Relaxation / drug effects*
  • Muscle Relaxation / physiology
  • Muscle, Smooth / drug effects*
  • Muscle, Smooth / physiology
  • Neurons / drug effects
  • Neurons / metabolism
  • Norepinephrine / pharmacokinetics
  • Norepinephrine / pharmacology
  • Parasympatholytics / pharmacology*
  • Prazosin / metabolism
  • Rats
  • Rats, Sprague-Dawley
  • Tritium
  • Vas Deferens / drug effects*
  • Vas Deferens / metabolism
  • Vas Deferens / physiology

Substances

  • Antitussive Agents
  • Aporphines
  • Calcium Radioisotopes
  • Hydroxylamines
  • Parasympatholytics
  • Tritium
  • methoxyamine
  • Calcium Chloride
  • glaucine
  • Calcium
  • Norepinephrine
  • Prazosin