Metabotropic glutamate receptor antagonists selectively enhance responses of slowly adapting type I mechanoreceptors

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Abstract
There is evidence that glutamate may participate as a transmitter at the junction between Merkel cells and the nerve terminals of slowly adapting type I (St I) units. We recorded extracellularly from the deep vibrissal nerve of an isolated rat vibrissa preparation in vitro. Five second trapezoid stimulus ramp deflections of the hair shaft were used to evoke responses. We bath‐applied two compounds, which we planned would interfere with glutamatergic transmission. (2S)‐2‐Amino‐2‐[(1S,2S)‐2‐carboxycycloprop‐1‐yl]‐3‐(xanth‐9‐yl) propanoic acid (LY341495) was used at concentrations up to 100 μM to block all known metabotropic glutamate (mGlu) receptors. The racemic mixture (RS)‐4‐carboxy‐3‐hydroxyphenylglycine ((RS)‐4C3HPG) was used up to 100 μM to block ionotropic and Group I metabotropic glutamate receptors, and as an agonist at Group II mGlu receptors. Unexpectedly, both compounds had rapid onset excitatory effects on mechanically‐evoked responses. (RS)‐4C3HPG increased responses, with a mean 146% of control (P< 0.05) in a concentration‐dependent manner. LY341495 increased responses, with a mean 128% of control (P< 0.05). With (RS)‐4C3HPG in particular, it was noted that the static component (the firing during the last 1 s plateau) was preferentially enhanced relative to the dynamic component (firing during the first 0.5 s). Rapid recovery was seen after wash. Slowly adapting type II units, which have no junctional transmission, were completely unaffected by these compounds up to 200 μM. These results suggest that mGlu receptors play a role in Merkel cell‐neurite complex mechanotransduction, although other explanations are considered. Synapse 59:235–242, 2006.