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	0.0015^ⁿ	48^ⁿ	2.9^ⁿ
9-Deoxy-neoDH	0.169^ⁿ	>100^ⁿ	>100^ⁿ
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.
↵a 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).
↵b Data from patch-clamp recordings in HEK293 cells transfected with rat receptors (Schiffer et al., 1997).
↵c Egebjerg et al. (1991).
↵d Schiffer et al. (1997).
↵e K_i values from displacement of [³H]kainate at human receptors (Jane et al., 1997).
↵f Data from willardiine-evoked currents from HEK293 cells expressing GluK2/GluK5 (Fukushima et al., 2001).
↵g 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).
↵h 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).
↵j Strange et al. (2006).
↵k Data from X. laevis oocytes treated with con A (Brehm et al., 2003).
↵l Data from Stensbøl et al. (2001).
↵m 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).
↵o 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).