Metabotropic Receptor Subtype Research Articles

Multiple ionic mechanisms are activated by the potent agonist quisqualate in cultured cerebellar Purkinje neurons

Current clamp recordings were used to analyze responses of cultured cerebellar Purkinje neurons to quisqualate and several other selectivenon- N-methyl- d-aspertate (NMDA) agonists. Quisqualate, a potent agonist in the cerebellar Purkinje neuron, evoked both short- and long-term changes in excitability, that activated within seconds and lasted for several minutes. Two components of the response were activated differentially by subtype selective agonists, and differed in their mechanism of expression and time course. The initial component of the response was activated by ionotropic agonists ((RS)-d-amino-3-hydroxyl-5-methyl-4-isoxazolepropionic acid (AMPA) domoate), and by quisqualate and glutamate which are effective at both the ionotropic and metabotropic quisqualate receptor subtypes, but not by the metabotropic agonist trans(±)-1amino-1,3-cyclopentanedicarboxylic acid (ACPD). This component was dependent on extracellular Na +, and characterized by a rapid depolarization with a short latency (<1–2 s) and a decrease in membrane resistance as expected for an ionotropic response. The rapid depolarization extended into an agonist-dependent plateau phase, which could not be evoked by depolarization alone. The second (‘late’) phase of the response was a slowly-activating, long-lasting change in membrane excitability, accompanied by little or no change in the membrane potential. The late phase, marked by an increase in voltage-dependent bursting spike activity, was induced by the metabotropic agonist, ACPD, and by quisqualate and glutamate, but not by ionotropic selective agonists such as AMPA. Little or no bursting was evoked by AMPA, domoate, kainate or homocysteate. This late phase was also accompanied by increases in the magnitude and duration of the complex spikes and in the afterhyperpolarization following brief current-driven depolarizations. The slower time course of the late component is consistent with a pathway involving second messenger systems. Our results support the hypothesis that coregulation of both ionotropic and metabotropic mechanisms produces the complex and prolonged excitatory response characteristic of the Purkinje neuron.

Ca2+ Mobilization in Cultured Rat Cerebellar Cells: Astrocytes are Activated by t-ACPD.

Using primary rat cerebellar cell cultures we observed that trans-1-amino-cyclopentyl-1,3-dicarboxylic acid (t-ACPD) was able to induce an increase in intracellular [Ca2+] in different cell types. This response was not abolished by external Ca2+ withdrawal, indicating that t-ACPD triggered the release of intracellularly stored Ca2+. In neurons the t-ACPD response was monophasic and inhibited by l-2-amino-4-phosphonobutyrate (APB). In astrocytes, characterized by their immunoreactivity to antisera to glial fibrillary acidic protein and S-100 protein, the response was oscillatory and resistant to APB application. These results suggest the presence of glutamate metabotropic receptor subtypes in the mammalian brain.

Vintage amino acid meeting describes new tools for amino acid research, subtypes of metabotropic receptors

Vintage amino acid meeting describes new tools for amino acid research, subtypes of metabotropic receptors