| Schistosoma mansoni muscle fibers contracted in response to L-glutamate in a dose-dependent manner (10{dollar}sp{lcub}-6{rcub}{dollar}-10{dollar}sp{lcub}-3{rcub}{dollar}M). D-Glutamate, L-aspartate and D-aspartate also caused contraction of the fibers. The glutamate receptor agonists NMDA, ibotenate, kainate, AMPA, quisqualate, ACPD, and L-AP-4 produced little or no contraction at concentrations as high as 1 mM. The glutamate receptor antagonists, MK-801, CNQX, AP-5, and MCPG, did not block glutamate responses. However, other amino acids, L-aspartate, L-cysteate, and cysteine sulfinate, were found to elicit contraction of the muscle fibers. Contraction induced by L-glutamate is dependent on extracellular Ca{dollar}sp{lcub}++{rcub}{dollar} and is blocked by the voltage-gated Ca{dollar}sp{lcub}++{rcub}{dollar} channel blocker nicardipine (10 and 1 {dollar}mu{dollar}M). ({dollar}sp3{dollar}H) -L-Glutamate, incubated with the muscle fiber preparation, was taken up in a dose-dependent manner, which is also time- and temperature-dependent. Both the L-glutamate induced contractile response of the fibers and ({dollar}sp3{dollar}H) -L-glutamate uptake are Na{dollar}sp+{dollar}-dependent, and can be blocked by specific inhibitors of the high-affinity transporter, DL-threo-{dollar}beta{dollar}-hydroxyaspartate, and L-trans-pyrollidine-2,4-dicarboxylic acid (THA, PDC). This pharmacology suggests that there may be an electrogenic glutamate transporter on the muscle fibers. It is possible that the electrogenic nature of the transporter is causing the fiber membrane to depolarize, thereby opening voltage-gated Ca{dollar}sp{lcub}++{rcub}{dollar} channels, and raising intracellular Ca{dollar}sp{lcub}++{rcub}{dollar} concentrations leading to contraction. This experimental evidence supports the hypothesis that there is a Na{dollar}sp+{dollar}-dependent high-affinity glutamate transporter on the schistosome muscle membrane. |
