Characterisation of a 5-HT(7) binding site in mouse ileum.
The aim of the present study was to identify 5-hydroxytryptamine(7) (5-HT(7)) binding sites in the mouse ileum, where the presence of mRNA for the receptor has been reported. Studies were performed using [3H]mesulergine, an antagonist with high affinity at 5-HT(7) receptors. In the presence of a combination of masking drugs to inhibit the binding of the radioligand to other receptors at which it has affinity, such as 5-HT(2A), 5-HT(2C) and dopamine D(2) receptors as well as alpha(1)/alpha(2)-adrenoceptors, [3H]mesulergine labelled two sites with pK(D) values of 9.7+/-0.7 and 7.4+/-0.4 and B(max) values of 37.2+/-21.4 and 247.8+/-62.1 fmol mg protein(-1), respectively. Displacement studies also indicated the presence of non-homogenous binding sites, which showed a significant correlation (Pearson correlation factors of 0.91 and 0. 85) with the 5-HT(2C) and 5-HT(7) receptors, respectively. Total binding to the 5-HT(2C) receptor was minimal; <30% of the total specific receptor binding. The antagonist order of affinity at the greater proportion of receptors was: risperidone (pK(i)pindolol (5. 6). This receptor also showed a high affinity for 5-carboxamidotryptamine (5-CT; 10.6) and moderate affinity for (+/-)-2-dipropyl-amino-8-hydroxy-1,2,3,4,-tetrahydronaphthalene (8-OH-DPAT; 7.2), which is typical of the 5-HT(7) receptor profile.
Hemedah
M
M
Department of Pharmaceutical Biology and Pharmacology, Victorian College of Pharmacy, Monash University (Parkville Campus), 381 Royal Parade, Parkville, Victoria 3052, Australia.
Coupar
I M
IM
Mitchelson
F J
FJ
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D004873:Ergolines / Q000378:metabolism*; D005260:Female; D007082:Ileum / Q000378:metabolism*; D008297:Male; D051379:Mice; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin / Q000378:metabolism*; D012701:Serotonin / Q000031:analogs & derivatives / Q000378:metabolism; D012702:Serotonin Antagonists / Q000378:metabolism*
D004873:Ergolines; D044405:Receptor, Serotonin, 5-HT2C; D011985:Receptors, Serotonin; D012702:Serotonin Antagonists; C104425:serotonin 7 receptor; D012701:Serotonin; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin; C047087:5-carboxamidotryptamine; C031649:mesulergine