PMID- 16968472
OWN - NLM
STAT- MEDLINE
DCOM- 20070316
LR  - 20171116
IS  - 1474-8665 (Print)
IS  - 1474-8665 (Linking)
VI  - 26
IP  - 4
DP  - 2006 Oct
TI  - Blockade of noradrenaline transport abolishes 4-methylthioamphetamine-induced 
      contraction of the rat aorta in vitro.
PG  - 335-44
AB  - The aim of this study was to characterize the effects of 4-methylthioamphetamine 
      (4-MTA) on contractility and noradrenaline (NA) transport and release in the 
      isolated rat aorta. Descending thoracic aortic rings were isolated from male 
      Wistar rats (220-240 g) and the effect of 4-MTA on contractility was measured by 
      isometric force displacement. 4-MTA (0.1 microm-1 mm) induced a 
      concentration-dependent contraction of aortic rings, with a pD(2) of 4.40 +/- 
      0.38, and an E(max) of 0.80 +/- 0.05 g tension. The alpha(1)-adrenoceptor 
      antagonist, prazosin (1 microm) and alpha(2) antagonist, yohimbine (1 microm) 
      inhibited maximal contraction to 100 microm 4-MTA by 45.0 +/- 6.7% and 53.5 +/- 
      7.1% of control values respectively, whereas the 5-hydroxytryptamine (5-HT) 
      antagonist, ketanserin (100 nm) had no effect on the 4-MTA-mediated contraction. 
      The specific NA transport inhibitor, nisoxetine (1 microm) abolished contraction 
      of the aorta by 4-MTA. 4 Nisoxetine-sensitive [(3)H]-NA transport in aortic rings 
      was measured over a concentration range of 0-5 microm [(3)H]-NA, and had a 
      maximal rate of transport (V(max)) of 0.77 +/- 0.07 pmol [(3)H]-NA min(-1) mg(-1) 
      protein and a Michaelis affinity constant (K(M)) of 2.3 +/- 0.5 microm. 4-MTA 
      inhibited nisoxetine-sensitive [(3)H]-NA transport with a pIC(50) of 6.16 +/- 
      0.18 and the pIC(50) for inhibition of nisoxetine-sensitive [(3)H]-NA transport 
      by 3,4-methylenedioxymethamphetamine (MDMA) was 6.83 +/- 0.13. 4-MTA (1-100 
      microm) significantly stimulated release of pre-loaded [(3)H]-NA from aortic 
      rings and 4-MTA-induced [(3)H]-NA release was inhibited by 1 microm nisoxetine. 
      These data suggest that 4-MTA causes contraction of the rat aorta in vitro by a 
      mechanism that is consistent with an ability to cause release of NA at the level 
      of the NA transporter. It is concluded that 4-MTA has the potential to increase 
      the extracellular concentration of NA peripherally as well as centrally, and that 
      this may cause adverse cardiovascular effects in its users.
FAU - Quinn, S T
AU  - Quinn ST
AD  - School of Biomolecular and Biomedical Science, UCD Conway Institute, University 
      College Dublin, Belfield, Dublin 4, Ireland.
FAU - Guiry, P J
AU  - Guiry PJ
FAU - Schwab, T
AU  - Schwab T
FAU - Keenan, A K
AU  - Keenan AK
FAU - McBean, G J
AU  - McBean GJ
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Auton Autacoid Pharmacol
JT  - Autonomic & autacoid pharmacology
JID - 101157306
RN  - 0 (Adrenergic Uptake Inhibitors)
RN  - 0 (Amphetamines)
RN  - 01K63SUP8D (Fluoxetine)
RN  - 10028-17-8 (Tritium)
RN  - 17NV064B2D (nisoxetine)
RN  - 6JP2T8KXTR (4-methylthioamphetamine)
RN  - KE1SEN21RM (N-Methyl-3,4-methylenedioxyamphetamine)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Adrenergic Uptake Inhibitors/pharmacology
MH  - Amphetamines/*pharmacology
MH  - Animals
MH  - Aorta, Thoracic/*drug effects/metabolism/physiology
MH  - Biological Transport/drug effects
MH  - Brain/cytology/drug effects/metabolism
MH  - Dose-Response Relationship, Drug
MH  - Fluoxetine/analogs & derivatives/pharmacology
MH  - In Vitro Techniques
MH  - Male
MH  - N-Methyl-3,4-methylenedioxyamphetamine/pharmacology
MH  - Norepinephrine/antagonists & inhibitors/*metabolism
MH  - Rats
MH  - Rats, Wistar
MH  - Synaptosomes/drug effects/metabolism
MH  - Tritium
MH  - Vasoconstriction/*drug effects
EDAT- 2006/09/14 09:00
MHDA- 2007/03/17 09:00
CRDT- 2006/09/14 09:00
PHST- 2006/09/14 09:00 [pubmed]
PHST- 2007/03/17 09:00 [medline]
PHST- 2006/09/14 09:00 [entrez]
AID - AAP373 [pii]
AID - 10.1111/j.1474-8673.2006.00373.x [doi]
PST - ppublish
SO  - Auton Autacoid Pharmacol. 2006 Oct;26(4):335-44. doi: 
      10.1111/j.1474-8673.2006.00373.x.