Parameter | Glutamate vs. MPEP^{a} | Glutamate vs. M-5MPEP^{a} | Glutamate vs. VU-29^{b} | Glutamate vs. DPFE^{b} | ||||
---|---|---|---|---|---|---|---|---|

eq. 3 | eq. 4 | eq. 3 | eq. 4 | eq. 3 | eq. 4 | eq. 3 | eq. 4 | |

pK_{A} [K_{A} (µM)] | 6.2 (0.6)^{c} | 6.2 (0.6)^{c} | 6.2 (0.6)^{c} | 6.2 (0.6)^{c} | 6.2 (0.6)^{c} | 6.2 (0.6)^{c} | 6.2 (0.6)^{c} | 6.2 (0.6)^{c} |

pK_{B} [K_{B} (µM)] | 7.9 ± 0.1 (0.01) | 8.4 ± 0.1 (0.004) | 6.8 ± 0.2 (0.2) | 6.8 ± 0.2 (0.2) | 6.7 ± 0.2 (0.2) | 6.7 ± 0.2 (0.2) | 6.0 ± 0.3 (1.0) | 5.6 ± 0.1 (2.5) |

Log τ_{A} (τ_{A}) | 0.7 ± 0.1 (5.0) | 1.0 ± 0.2 (10) | 0.6 ± 0.1 (3.9) | 0.6 ± 0.2 (4.0) | 0.7 ± 0.03 (5.0) | 0.7 ± 0.1 (5.0) | 0.6 ± 0.1 (4.0) | 0.8 ± 0.1 (6.3) |

Log τ_{B} (τ_{B}) | n.a. (0) | n.a. (0) | n.a. (0) | n.a. (0) | n.a. (0) | n.a. (0) | −0.2 ± 0.1 (0.6) | −0.4 ± 0.1 (0.4) |

Log αβ (αβ) | −100 (∼0)^{d} | −100 (∼0)^{d} | −0.5 ± 0.1 (0.3) | −0.8 ± 0.2 (0.2) | 0.3 ± 0.03 (2.0) | 0.3 ± 0.04 (0.2) | 0.6 ± 0.1 (4.0) | 1.1 ± 0.1 (13) |

n | 1.7 ± 0.2^{e} | 1.5 ± 0.2^{e} | 2.0 ± 0.2^{e} | 1.6 ± 0.2^{e} | 1.3 ± 0.1^{e} | 1.2 ± 0.1^{e} | 2.5 ± 0.7^{e} | 1.3 ± 0.1^{e} |

E_{m} (% glutamate) | 106 ± 6.0 | 111 ± 6.0 | 107 ± 6.0 | 123 ± 1.0 | 108 ± 3.0 | 111 ± 3.0 | 107 ± 2.0 | 105 ± 2.0 |

Dfd, degrees of freedom denominator; Dfn, degrees of freedom numerator;

*E*_{m}, maximum system response; Log*αβ*(*αβ*), modulator cooperativity; Log*τ*_{A}(*τ*_{A}), glutamate efficacy; Log*τ*_{B}(*τ*_{B}), modulator efficacy;*n*, transducer or binding slope; n.a., no agonist activity [log*τ*_{B}fixed to −100 (*τ*_{B}0)]; p*K*_{A}(*K*_{A}), agonist affinity; p*K*_{B}(*K*_{B}), modulator affinity.↵

^{a}Values derived by fitting previously reported experimental data (Sengmany et al., 2019).↵

^{b}Values derived by fitting previously reported experimental data (Sengmany et al., 2017).↵

^{c}The p*K*_{A}value was fixed to that determined in radioligand binding assays (Mutel et al., 2000).↵

^{d}The log*αβ*value was fixed to −100 due to complete inhibition of glutamate-mediated stimulation of Ca^{2+}_{i}mobilization, reflecting high negative cooperativity.↵

^{e}An*F*test determined that data were fitted best when the transducer or binding slopes were different from unity. The*F*data used to test the hypothesis that*n*differed from 1 were the following: eq. 3 MPEP*P*= 0.0003,*F*[(Dfn, Dfd) 13.46 (1, 149)]; eq. 3 M-5MPEP*P*= 0.0007,*F*[(Dfn, Dfd) 11.96 (1, 126)]; eq. 3 VU-29*P*= 0.0015,*F*[(Dfn, Dfd) 10.45 (1, 144)]; eq. 3 DPFE*P*= 0.0062,*F*[(Dfn, Dfd) 7.587 (1, 294)]; eq. 4 MPEP*P*= 0.0002,*F*[(Dfn, Dfd) 14.33 (1, 149)]; eq. 4 M-5MPEP*P*< 0.0001,*F*[(Dfn, Dfd) 22.26 (1, 126)]; eq. 4 VU-29*P*= 0.0003,*F*[(Dfn, Dfd) 13.97 (1, 144)]; and eq. 4 DPFE*P*< 0.0001,*F*[(Dfn, Dfd) 24.13 (1, 294)].