Effect of tuamine, heptaminol and two analogues on uptake and release of catecholamines in cultured chromaffin cells.
The effects of tuamine (1-methylhexylamine), a sympathomimetic compound with hypertensive properties, heptaminol (6-amino-2-methyl-2-heptanol), an aliphatic amine with pressor properties, and two structural analogues of tuamine on high-affinity Na(+)-dependent noradrenaline uptake and on nicotine-evoked release were examined in bovine chromaffin cells maintained in primary culture for 3 to 6 days. Tuamine was found to be a potent competitive inhibitor of noradrenaline uptake with an effect similar to that of cocaine. Its inhibition constant (Ki) was 1.1 +/- 0.1 microM while Ki values of heptaminol, of 1-methylamino-5-pentanol oxalate and of 5-amino-2-methylhexanol oxalate, which were also found to be competitive inhibitors of noradrenaline uptake, were 60 +/- 2 microM, 260 +/- 28 microM and 48 +/- 76 microM, respectively. Tuamine, hepataminol and 5-amino-2-methyl-2-hexanol were also shown to be inhibitors of nicotine-induced release of catecholamines, with IC50 values of 26 +/- 2 microM, 650 +/- 11 microM and 500 +/- 10 microM, respectively. Tuamine and hepataminol did not inhibit noradrenaline release evoked by 59 mM K+, suggesting that it acts at a step prior to calcium entry. The pharmacological properties of heptaminol as an anti-hypotension agent may partially account for its inhibitory effect on catecholamine uptake and release.
Delicado
E G
EG
Departamento de Bioquimica, Facultad de Veterinaria, Universidad Complutense, Madrid, Spain.
Fideu
M D
MD
Miras-Portugal
M T
MT
Pourrias
B
B
Aunis
D
D
D000588:Amines / Q000494:pharmacology*; D000605:Amino Alcohols / Q000494:pharmacology*; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D002837:Chromaffin Granules / Q000187:drug effects / Q000378:metabolism*; D002838:Chromaffin System / Q000378:metabolism*; D006535:Heptaminol / Q000494:pharmacology*; D009538:Nicotine / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013566:Sympathomimetics / Q000494:pharmacology*
D000588:Amines; D000605:Amino Alcohols; D013566:Sympathomimetics; D006535:Heptaminol; D009538:Nicotine; D009638:Norepinephrine; C065369:tuaminoheptane