Effect of PCP and sigma ligands on both noradrenaline- and electrically-induced contractions and on [3H]-noradrenaline uptake in rat vas deferens.
1. Electrically induced contractions of the epididymal portion of rat vas deferens were potentiated in concentration-dependent manner (0.1-30 microM) by different sigma and PCP receptor ligands (PCP, TCP, (+)-MK-801, dextromethorphan and (+)-3-PPP); dextrorphan did it in a minor extent. 2. Sigma and PCP receptor ligands also potentiated the effect of noradrenaline, inducing a reduction of the noradrenaline EC50 value in the rat vas deferens. The rank order of potencies was: PCP > TCP > (+)-3-PPP > (+)-MK-801 > dextrorphan > > > dextrometorphan. 3. In contrast, haloperidol (1 microM), a sigma receptor ligand, inhibited both the neurogenic and noradrenaline-induced responses in this tissue. 4. The effect of PCP and sigma receptor ligands on noradrenaline uptake was evaluated. All compounds tested, including haloperidol, inhibited the tritiated noradrenaline incorporation to the tissue. IC50 values were in the micromolar range, between 1.09 microM for dextrophan and 18 microM for dextrometorphan. 5. It is concluded that a direct interaction with the noradrenaline uptake system is involved in the potentiating effect of some sigma and PCP receptor ligands in the epididymal portion of rat vas deferens.
Pubill
D
D
Unitat de Farmacologia i Farmacognòsia, Facultat de Farmàcia, Universitat de Barcelona, Spain.
Canudas
A M
AM
Sureda
F X
FX
Camins
A
A
Pallas
M
M
Escubedo
E
E
Camarasa
J
J
D000316:Adrenergic alpha-Agonists / Q000493:pharmacokinetics* / Q000494:pharmacology*; D000818:Animals; D003915:Dextromethorphan / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism / Q000494:pharmacology; D018491:Dopamine Agonists / Q000378:metabolism / Q000494:pharmacology; D004558:Electric Stimulation; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism / Q000494:pharmacology; D008024:Ligands; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D018696:Neuroprotective Agents / Q000378:metabolism / Q000494:pharmacology; D009638:Norepinephrine / Q000493:pharmacokinetics* / Q000494:pharmacology*; D010622:Phencyclidine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D010880:Piperidines / Q000378:metabolism / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017478:Receptors, Phencyclidine / Q000187:drug effects / Q000378:metabolism*; D017480:Receptors, sigma / Q000187:drug effects / Q000378:metabolism*; D014316:Tritium; D014649:Vas Deferens / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D018491:Dopamine Agonists; D018691:Excitatory Amino Acid Antagonists; D008024:Ligands; D018696:Neuroprotective Agents; D010880:Piperidines; D017478:Receptors, Phencyclidine; D017480:Receptors, sigma; D014316:Tritium; D016291:Dizocilpine Maleate; D003915:Dextromethorphan; C012058:tenocyclidine; C026539:preclamol; D010622:Phencyclidine; D009638:Norepinephrine