TABLE 2.

Potency for substrates and inhibitors in inhibiting [³H]DA uptake in hNET and hDAT mutants

Data were calculated as a percentage of uptake in the absence of competing substrate or inhibitor and analyzed by nonlinear regression. Data displayed in the table are IC₅₀ values with confidence intervals (CI) given in parentheses (n = 3–6). Statistical significance was determined by an F test by comparing fits in which selected values were constrained to be equal or were allowed to differ. The null hypothesis was that the best-fit parameter for the value did not differ. A conclusion of statistical significance represents a rejection of the null hypothesis and indicates a difference between designated values

	hNET	T58A-hNET	T58D-hNET	hDAT	T62A-hDAT	T62D-hDAT
	nM
Substrates
DA	340	230*	6***	2510	680*	54***
(n = 3)	(280–410)	(180–300)	(2–20)	(1250–5000)	(270–1700)	(18–160)
		F1,30 = 4.694	F1,30 = 206.6		F1,29 = 6.544	F1,29 = 50.77)
NE	550	370	70***	12,600	7500	590***
(n = 3)	(350–850)	(140–900)	(50–90)	(7900–20,000)	(5500–10,000)	(460–760)
			F1,30 = 63.95			F1,30 = 128.1
AMPH	59	37*	5***	310	130**	12***
(hNET, n = 3; hDAT, n = 6)	(43–82)	(28–48)	(3.4–5.9)	(270–350)	(120–150)	(9–17)
		F1,30 = 4.80	F1,30 = 140.4		F1,30 = 11.93	F1,30 = 62.33
Inhibitors
Cocaine	3970	3180	6240	260	300	1130**
(hNET, n = 3; hDAT, n = 6)	(2000–7900)	(1470–6880)	(3500–11,300)	(130–510)	(180–510)	(540–2400)
						F1,64 = 9.261
Benztropine	3730	4760	9250	140	170	1240***
(hNET, n = 3; hDAT, n = 6)	(2060–6750)	(2250–10,000)	(3600–23,300)	(65–310)	(120–250)	(540–2800)
						F1,64 = 19.86
Nisoxetine	32	30	16	N.D.	N.D.	N.D.
(n = 3)	(20–50)	(13–73)	(6–40)
Desipramine	19	15	12	N.D.	N.D.	N.D.
(n = 3)	(12–30)	(8–29)	(8–17)
GBR12935	N.D.	N.D.	N.D.	105	109	191
(n = 6)				(81–135)	(51–231)	(90–388)

^*P < 0.05 compared with wild-type value.

^**P < 0.01 compared with wild-type value.

^***P < 0.001 compared with wild-type value.