Choudhary S , Abongwa M , Kashyap SS , Verma S , Mair GR , Kulke D , Martin RJ , Robertson AP .

NA Bayer Animal Health GmbH, R21 AI092185 NIAID NIH HHS , R21 AI125899 NIAID NIH HHS , R01 AI047194 NIAID NIH HHS , R01 AI155413 NIAID NIH HHS , R21 AI173819 NIAID NIH HHS

Figure 5. Effect of NA on the Xenopus oocytes expressing B. malayi AVR-14B. (A) Representative inward current responses from oocyte challenged with increasing concentrations of NA (n ≥ 5). (B) Representative inward current response from oocyte used for studying the positive modulatory effect of NA on L-glutamate (30 µM) gated current response (n ≥ 5). (C) Example of peak current and AUC measurements of the traces to quantify the PAM effect of NA on L-glutamate gated current response. (D) Concentration-response relationship curves for L-glutamate, NA, and NA in the presence of 30 µM L-glutamate when normalized to 30-mM L-glutamate current response. EC50 and nH were 0.4 mM (pEC50 = 3.4 ± 0.2) and 0.8 ± 0.3 for L-glu, respectively; 2.7 µM (pEC50 5.6 ± 0.2) and 1.6 ± 0.8 for NA, respectively. The estimated minimum EC50 and nH for NA in the presence of 30 µM L-glu was 0.4 µM (pEC50 = 6.4 ± 0.4) and 0.8 ± 0.4, respectively. Bottom was constrained to zero. (E) Concentration-response relationship curves for L- glutamate, NA, and NA in the presence of 30 µM L- glutamate when normalized to 30-mM L- glutamate AUC response. AUC (max) ± SEM, %, was 154.7 ± 10.4 for L- glutamate; 999.4 ± 227.1 for NA; 1430.0 ± 168.3 for NA in the presence of 30 µM L-glutamate. L-glu, L-glutamate. Error bars in D and E represent SEM.

Figure 6. IVM acts as an inhibitor of NA-mediated potentiation of L-glutamate–gated currents in the Xenopus oocytes expressing B. malayi AVR-14B. (A) Representative inward current responses showing the effect of IVM (0.1 nM IVM in top trace, n = 6; 1 pM in bottom trace; n = 6) on combination of NA with L- glutamate (L-glu; 30 µM). (B) Concentration-response curves showing the potent inhibitory effect of 0.1 nM IVM on combination of NA (0.1 to 0.3 µM) with L-glutamate (30 µM) when normalized to 30-mM L-glutamate current response. (C) Concentration-response curves showing effect of 1 pM IVM on combination of NA (0.1 to 3 µM) with L-glutamate (30 µM) when normalized to 30-mM L-glutamate current response. EC50 values were 0.4 µM (pEC50 = 6.4 ± 0.4) for NA and L-glutamate combination in the absence of IVM; 0.3 µM (pEC50 = 6.5 ± 1.0) NA and L-glutamate combination in the presence of IVM. There was no significant difference between the Hill slopes. (D) Concentration-response curves showing effect of 1 pM IVM on combination of NA (0.1 to 3 µM) with L-glutamate (30 µM) when normalized to 30-mM L-glutamate AUC response. AUC (max) ± SEM, %, was 1,430.0 ± 168.3 for NA and L-glutamate combination in the absence of IVM; 295.5 ± 101.0 for NA and L-glutamate combination in the presence of IVM. L-glu, L-glutamate. Error bars in B and C represent SEM.

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