. 2010 Sep;62(3):405–496. doi: 10.1124/pr.109.002451

TABLE 6.

Kainate receptor agonist EC₅₀ values in micromolar

Agonist	GluK1	GluK2	GluK3	GluK1/GluK2	GluK1/GluK5	GluK2/GluK5
	μM
l-Glutamate	47^a	9^a	5900^b	48^a	19^a	8^a
AMPA	208^a	N.E.^c	N.E.^d	154^a	123^a	137^a
Kainate	4.9^a	1.1^a		7.4^a	1.5^a	0.6^a
Willardiine	28.9^e					127^f
F-Willardiine	1.8^e
Cl-Willardiine	0.057^e
Br-Willardiine	0.0091^e
I-Willardiine	0.21^a	N.E.^a		0.47^a	0.06^a	30^a
(S)-ATPA	0.33^a	N.E.^a		0.8^a	0.38^a	106^a
SYM2081	0.18^a	0.29^a		0.38^a	0.06^a	0.34^a
Domoic acid	0.36^a	0.07^a		0.19^a	0.05^a	0.12^a
LY339434	2.5^g	>100^g			-
Dysiherbaine	0.0005^h	0.0013^h			N.D.ⁱ
neoDH	0.008^h	0.03^h
ACPA	22^j	101^j
(S)-4-AHCP	0.13^k	N.E.^k				6.4^k
(S)-Thio-ATPA	0.1^l	N.E.^l				4.9^l
2-Me-Tet-AMPA	8.7^m					15.3^m
8-Deoxy-neoDH	0.0015ⁿ	48ⁿ	2.9ⁿ
9-Deoxy-neoDH	0.169ⁿ	>100ⁿ	>100ⁿ
MSVIII-19	3.6^o	N.E. (>100)^o

ACPA, (R,S)-2-amino-3-(3-carboxy-5-methyl-4-isoxazolyl)propionic acid; (S)-4-AHCP, (R,S)-2-amino-3-(3-hydroxy-7,8-dihydro-6H-cyclohepta[d]isoxazol-4-yl)propionic acid; AMPA, α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid; 2-Me-Tet-AMPA, 2-amino-3-[3-hydroxy-5-(2-methyl-2H-tetrazol-5-yl)isoxazol-4-yl]propionic acid; (S)-ATPA, (S)-2-amino-3-(5-tert-butyl-3-hydroxyisoxazol-4-yl)propionic acid; (S)-thio-ATPA, (S)-2-amino-3-(5-tert-butyl-3-hydroxy-4-isothiazolyl)propionic acid; N.D., not determined; N.E., no effect; neoDH, neodysiherbaine.

Data from calcium influx (fluorometric imaging plate reader) in HEK293 cells stably transfected with human receptors and treated with con A (Alt et al., 2004).

Data from patch-clamp recordings in HEK293 cells transfected with rat receptors (Schiffer et al., 1997).

Egebjerg et al. (1991).

Schiffer et al. (1997).

K_i values from displacement of [³H]kainate at human receptors (Jane et al., 1997).

Data from willardiine-evoked currents from HEK293 cells expressing GluK2/GluK5 (Fukushima et al., 2001).

Data from patch-clamp recordings in HEK293 cells stably transfected with human receptors and treated with con A. EC₅₀ of LY339434 at isolated dorsal root ganglion, cerebellar Purkinje cells and cultured hippocampal neurons was 0.8, 362, and 2.5 μM, respectively. The EC₅₀ of LY339434 at GluA1, GluA2, and GluA4 receptors was greater than 10,000 μM (Small et al., 1998).

Data for dysiherbaine and neodysiherbaine are K_i values based on inhibition of [³H]kainate binding to receptors expressed in HEK293 cells from Sakai et al. (2001b) and Sanders et al. (2005), respectively. The K_i for dysiherbaine binding to neuronal AMPA receptors was 26–153 μM (Sakai et al., 2001b).

ⁱ

GluK1/GluK5 receptors were proposed to have a high-affinity dysiherbaine binding site at GluK1 and a low-affinity site at GluK5. Supporting this, dysiherbaine bound to homomeric GluK5 receptors with a K_i of 4.9 μM (Swanson et al. 2002).

Strange et al. (2006).

Data from X. laevis oocytes treated with con A (Brehm et al., 2003).

Data from Stensbøl et al. (2001).

Data from X. laevis oocytes (Vogensen et al., 2000).

ⁿ

Although both 8-deoxy-neoDH and 9-deoxy-neoDH elicited current from GluK1 receptors, their potencies were reported as K_i values calculated from IC₅₀ values for displacing [³H]kainate at recombinant kainate receptors (Lash et al., 2008).

EC₅₀ for MSVIII-19 at GluK1 recombinant receptors expressed in HEK293 cells treated with Con A. MSVIII-19 failed to displace kainate from recombinant GluK2 expressed in HEK293 cells (Frydenvang et al., 2009).