Table II.

Relative Inverse Affinities of Substrates and Inhibitors of VMAT in Heterologous Expression Systems

Substrate/Inhibitor		hVMAT1a	hVMAT2a	rCGVMATb	bVMAT2c	Chromaffin Granulesd
1	5HT	1.4 ± 0.2	0.9 ± 0.1	0.85 ± 0.023	0.59	0.4
2	DA	3.8 ± 0.4	1.4 ± 0.2	1.56 ± 0.035	1.4	-
3	NE	13.7 ± 1.6	3.4 ± 0.5	2.5 ± 0.04	1.7	1.4
4	E	5.5 ± 0.7	1.9 ± 0.2	1.86 ± 0.011	2.5	1.4
5	Tetrabenazine(TBZ)	>20	0.097 ± 0.002		0.027
6	Reserpine (RES)	0.034 ± 0.005	0.012 ± 0.003		0.0007
7	Ketanserine (KET)	1.7 ± 0.2	0.54 ± 0.07		0.170
9	Histamine	4500 ± 600	143 ± 12	436 ± 36	-
10	Phenylethylamine	34 ± 5	3.7 ± 0.5
11	Amphetamine (+)	47 ± 6	2.1 ± 0.2
12	Amphetamine (−)	259 ± 33	10 ± 1.7
13	MDMA (+/−)	19 ± 3	6.9 ± 1.0
14	Fenfluramine	3.1 ± 0.4	5.1 ± 0.5
15	MPP+	69 ± 10	8.9 ± 1.4		9.7	1.5

^aDetermined using digitonin permiabilized CV-1 cells expressing c DNA of hVMAT1 and hVMAT2 in the presence of ATP. The apparent K_m and V_max parameters determined with [³H]5HT for VMAT1 and VMAT2 were 1.3 μM and 0.8 μM and 37 and 43 pmoles/min.450,000 cells, respectively. Inhibition of [3H]5HT uptake (90 nM) in the presence of various substrates were determined and Ki values were estimated by nonlinear regression analysis²⁰.

^bDetermined using the membranes prepared from the COS cells transfected with hCGVMAT in the presence of ATP. The apparent K_m determined for [3H]5HT uptake was 0.3 μM. Inhibition of [³H]5HT uptake in the presence of various substrates were determined and K_i values were estimated by nonlinear regression analysis⁴¹.

^cDetermined using homogenized COS cells expressing c DNA of bVMAT2 in the presence of ATP. The apparent K_m and V_max parameters were determined for [³H] norepinephrine were 1.9 μM and 32 pmoles/min.mg. The affinities of the substrates with respect to [³H] norepinephrine (IC₅₀ values) were estimated by competitive experiments⁴².

^dTaken from the ref. 42.