title: GABA(C) receptor antagonists differentiate between human rho1 and rho2 receptors expressed in Xenopus oocytes.
abstract: The selective GABA(C) receptor antagonist, (1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid (TPMPA), is eight times more potent against human recombinant p receptors than p2 receptors expressed in Xenopus oocytes. (3-Aminopropyl)methylphosphinic acid (CGP35024), the methylphosphinic acid analogue of GABA, and [(E)-3-aminopropen-1-yl]methylphosphinic acid (CGP44530), an open chain analogue of TPMPA, were five and four times, respectively, more potent as antagonists of p1 receptors than as antagonists of p2 receptors. Isoguvacine was a weak partial agonist at both p1 and p2 receptors with intrinsic activities (calculated as a percentage of the maximum whole cell current produced by a maximum dose of GABA) of 45 and 68%, respectively, of the maximum response produced by GABA. In agreement with other workers, it was found that imidazole-4-acetic acid was a partial agonist at both p1 and p2 receptors, showing higher intrinsic activity at p2 than at p1 receptors. The p1 receptor antagonist, trans-4-amino-2-methylbut-2-enoic acid (2-MeTACA), was a partial agonist at p2 receptors with an intrinsic activity of 34%. 2-MeTACA may be useful in differentiating between homo-oligomeric p1 and p2 receptors in native systems. These studies reveal significant differences in the antagonist profile of human recombinant p1 and p2 GABA(C) receptors.
authors.affiliation: Department of Pharmacology, The University of Sydney, NSW, Australia. maryc@pharmacol.usyd.edu.au
authors.forename: M
authors.initials: M
authors.lastname: Chebib
authors.forename: K N
authors.initials: KN
authors.lastname: Mewett
authors.forename: G A
authors.initials: GA
authors.lastname: Johnston
mesh_terms: D000818:Animals; D018756:GABA Antagonists / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D009865:Oocytes / Q000502:physiology*; D010721:Phosphinic Acids / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D018079:Receptors, GABA / Q000145:classification*; D011994:Recombinant Proteins / Q000378:metabolism; D014981:Xenopus
chemical_list: C101879:(1,2,5,6-tetrahydropyridin-4-yl)methylphosphinic acid; D018756:GABA Antagonists; D010721:Phosphinic Acids; D011725:Pyridines; D018079:Receptors, GABA; D011994:Recombinant Proteins