Study of the mechanism of the relaxant action of (+)-glaucine in rat vas deferens.
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.
Orallo
F
F
Departamento de Farmacología, Facultad de Farmacia, Universidad de Santiago de Compostela, Spain.
Fernández Alzueta
A
A
Loza
M I
MI
Vivas
N
N
Badía
A
A
Campos
M
M
Honrubia
M A
MA
Cadavid
M I
MI
D000818:Animals; D000996:Antitussive Agents / Q000494:pharmacology*; D001060:Aporphines / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000493:pharmacokinetics; D002122:Calcium Chloride / Q000494:pharmacology; D002132:Calcium Radioisotopes; D002462:Cell Membrane / Q000378:metabolism; D004558:Electric Stimulation; D006898:Hydroxylamines / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects / Q000502:physiology; D009126:Muscle Relaxation / Q000187:drug effects* / Q000502:physiology; D009130:Muscle, Smooth / Q000187:drug effects* / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009638:Norepinephrine / Q000493:pharmacokinetics / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D011224:Prazosin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D014316:Tritium; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology
D000996:Antitussive Agents; D001060:Aporphines; D002132:Calcium Radioisotopes; D006898:Hydroxylamines; D010276:Parasympatholytics; D014316:Tritium; C005214:methoxyamine; D002122:Calcium Chloride; C005004:glaucine; D002118:Calcium; D009638:Norepinephrine; D011224:Prazosin