Vascular actions of 3,4-methylenedioxymethamphetamine in alpha(2A/D)-adrenoceptor knockout mice.
We have investigated the effects of 3,4-methylenedioxymethamphetamine (MDMA) on mean arterial pressure in anaesthetised wild-type and alpha(2A/D)-adrenoceptor knockout mice. In wild-type mice, MDMA (5 mg kg(-1)) produced a pressor response that declined to baseline by 2 min and fell below baseline to a depressor response by 5 min, whereas MDMA (20 mg kg(-1)) produced only a pressor response that declined to baseline by 5 min. In wild-type mice, following the injection of the selective alpha(2A/D)-adrenoceptor antagonist, 2-((4,5-dihydro-1H-imidazole-2-yl)methyl)-2,3-di-hydro-1-methyl-1H-isoindole (BRL44408), the peak pressor response to MDMA (5 or 20 mg kg(-1)) was not modified but durations of the pressor effects of both doses of MDMA were prolonged with responses significantly above baseline at 5 min. In alpha(2A/D)-adrenoceptor knockout mice, the peak response to MDMA (5 mg kg(-1)) was similar to that in wild-type but the response fell to baseline over 5 min with no depressor component, whereas MDMA (20 mg kg(-1)) produced a sustained pressor response significantly above baseline at 10 min. The responses were similar to those obtained in wild-type in the presence of BRL44408. It is concluded that MDMA produces depressor responses in wild-type mice by action at alpha(2A/D)-adrenoceptors to shorten the duration of the pressor response.
Vandeputte
Catherine
C
Department of Physiology, Royal College of Surgeons in Ireland, 123 St Stephen's Green, 2, Dublin, Ireland.
Docherty
James R
JR
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology*; D058647:Adrenergic alpha-2 Receptor Agonists; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D054833:Isoindoles; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000494:pharmacology*; D018341:Receptors, Adrenergic, alpha-2 / Q000235:genetics / Q000502:physiology*; D013997:Time Factors
C547769:Adra2a protein, mouse; D018759:Adrenergic Uptake Inhibitors; D058647:Adrenergic alpha-2 Receptor Agonists; D000317:Adrenergic alpha-Antagonists; D007093:Imidazoles; D007211:Indoles; D054833:Isoindoles; D018341:Receptors, Adrenergic, alpha-2; D018817:N-Methyl-3,4-methylenedioxyamphetamine; C072125:BRL 44408