Selective activation of phosphoinositide hydrolysis by a rigid analogue of glutamate

Ibotenate and trans-D,L-1-amino-1,3-cyclopentanedicarboxylic acid (trans-ACPD) are rigid analogues of glutamate. Ibotenate has been shown to activate phosphoinositide hydrolysis in rat brain slices. We now report that trans-ACPD also stimulates phosphoinositide hydrolysis but with much higher potency and efficacy than ibotenate. The pharmacological profiles, regional distributions, and developmental regulation of the responses to ibotenate and trans-ACPD are similar, suggesting that these agonists act at the same site. However, trans-ACPD is the first agonist described that is selective for this receptor relative to other excitatory amino acid receptor subtypes.