Pharmacological comparison of the rat and guinea-pig cortical high affinity 5-hydroxytryptamine uptake system.
The pharmacological characteristics of the high affinity [3H]5-hydroxytryptamine ([3H]5-HT) uptake system were investigated in the cerebral cortex of the rat and guinea-pig. In crude cortical synaptosomal preparations from the rat and guinea-pig, [3H]5-HT accumulated with high affinity (Km, 72 +/- 12 and 57 +/- 14 nM for rat and guinea-pig cortical synaptosomal preparation, respectively, mean +/- SEM, N = 5) and with a comparable maximum activity (Vmax, 1.22 +/- 0.21 and 0.90 +/- 0.19 pmol/min/mg protein for rat and guinea-pig cortical synaptosomal preparation, respectively, mean +/- SEM, N = 5). Competition studies employing a range of structurally diverse competing compounds showed that the [3H]5-HT uptake was pharmacologically similar in both preparations. However, citalopram possessed approximately 10-fold weaker affinity to prevent [3H]5-HT uptake in the guinea-pig preparation when compared to the rat and all of the tricyclic antidepressants assessed in the present studies (amitriptyline, nortriptyline, desipramine and imipramine) displayed higher affinity in the guinea-pig preparation when compared to the rat. It is concluded that the high affinity 5-HT uptake systems in the rat and guinea-pig cortex are similar but may not be identical.
Hornsby
C D
CD
School of Pharmacy, University of Bradford, U.K.
Barnes
J M
JM
Barnes
N M
NM
Champaneria
S
S
Costall
B
B
Naylor
R J
RJ
D000639:Amitriptyline / Q000494:pharmacology; D000818:Animals; D001667:Binding, Competitive; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D015283:Citalopram / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D005260:Female; D006168:Guinea Pigs; D007700:Kinetics; D009661:Nortriptyline / Q000494:pharmacology; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism
D015283:Citalopram; D000639:Amitriptyline; D012701:Serotonin; D009661:Nortriptyline; D003891:Desipramine