GABA(B) auto- versus hetero-receptor sensitivity: implications for novel pharmacotherapy.
After uncoupling G-protein dependent post-synaptic GABA(B) receptors--without altering GABA(B) nerve terminal receptors--we demonstrate that the GABA(B) agonist, CGP44533, exhibits less efficacy and potency at GABA(B) auto- versus hetero-receptors. CGP44533 (1 and 10 microM) depressed monosynaptic GABA(A)-mediated transmission by 2 and 35%, but depressed glutamate mediated transmission by 41 and 78%, respectively. These data suggest a differential pharmacological sensitivity for CGP44533 at glutamate versus GABA releasing neurons.
Yu
B
B
Department of Pharmacology and Toxicology, University of Texas Medical Branch, Galveston 77555-1031, USA.
Yamada
K
K
Gallagher
J P
JP
D000818:Animals; D017660:Autoreceptors / Q000187:drug effects* / Q000378:metabolism; D018755:GABA Agonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000187:drug effects / Q000378:metabolism; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018408:Patch-Clamp Techniques; D051381:Rats; D017207:Rats, Sprague-Dawley; D018080:Receptors, GABA-B / Q000187:drug effects* / Q000378:metabolism; D012686:Septal Nuclei / Q000187:drug effects* / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*
D017660:Autoreceptors; D018755:GABA Agonists; D018080:Receptors, GABA-B; D018698:Glutamic Acid