Transport characteristics of guanidino compounds at the blood-brain barrier and blood-cerebrospinal fluid barrier: relevance to neural disorders

Table 1 Inhibitory effect of various compounds on [¹⁴C]GAA uptake by HEK293 cells stably overexpressing CRT (CRT/HEK293 cells) and Xenopus oocytes expressing CRT (CRT/oocytes) or TauT (TauT/oocytes), and [¹⁴C]CTN uptake by Xenopus oocytes expressing rOCT3(rOCT3/oocytes).

Inhibitor		[¹⁴C]GAA uptake		[¹⁴C]CTN uptake
	CRT/HEK293 cells %of control	CRT/oocytes %of control	TauT/oocytes %of control	rOCT3/oocytes %of control
Control	100 ± 4	100 ± 9	100 ± 9	100 ± 19
Guanidinoacetate (GAA)	19.2 ± 2.6*	44.6 ± 2.7*	53.2 ± 9.6*	-
β-Guanidinopropionate (GPA)	1.81 ± 0.14*	0.944 ± 0.189*	4.77 ± 0.66*	143 ± 21
γ-Guanidinobutyrate (GBA)	10.0 ± 0.6*	21.4 ± 2.0*	21.7 ± 4.2*	-
Guanidinoethansulfonate (GES)	23.1 ± 1.1*	-	4.66 ± 0.22*	-
Guanidinosuccinate (GSA)	101 ± 1	107 ± 12	103 ± 10	-
Creatine (CT)	3.06 ± 0.24*	2.91 ± 0.23*	98.4 ± 12.7	137 ± 24
Taurine	111 ± 5	-	3.00 ± 0.19*	-
γ-Aminobutyric acid (GABA)	95.5 ± 2.9	-	34.0 ± 4.6*	-
Creatinine (CTN)	93.3 ± 5.3	123 ± 10	97.9 ± 14.6	-
Methylguanidine (MG)	82.3 ± 15.2	126 ± 14	110 ± 18	47.2 ± 18.9**
Creatine phosphate (PCT)	93.4 ± 6.8	97.9 ± 14.1	117 ± 6	-
Guanidine	114 ± 6	88.2 ± 13.4	-	137 ± 22
L-Arginine	86.6 ± 6.3	-	-	-
Glycine	126 ± 4	-	-	-
L-Alanine	111 ± 3	-	-	-
L-Aspartic acid	98.5 ± 2.2	-	-	-
Tetraethylammonium	128 ± 29	82.8 ± 7.3	-	48.1 ± 8.3**
Benzylpenicillin	110 ± 14	115 ± 12	-	-

[¹⁴C]GAA (20-45 μM) and [¹⁴C]CTN (70 μM) uptake by CRT/oocytes, TauT/oocytes and rOCT3/oocytes was measured at 20°C for 60 min in the absence (control) or presence of inhibitors (2 mM). [¹⁴C]GAA (3 μM) uptake by CRT/HEK293 cells was measured at 37°C for 5 min in the absence (control) or presence of inhibitors (2 mM). Each value represents the mean ± SEM (n = 4-8 for CRT/HEK293 cells, n = 10-25 for CRT/oocytes, TauT/oocytes and rOCT3/oocytes). *p < 0.01, **p < 0.05, significantly different from control. -, not determined.
Modified and reproduced from Tachikawa et al. [50, 51, 56].

ISSN: 2045-8118