Differing actions of nitropropane analogs of GABA and baclofen in central and peripheral preparations.
In the guinea-pig isolated ileum, both baclofen (5-100 microM) and gamma-aminobutyric acid (GABA; 5-100 microM) induced a bicuculline-insensitive depression of cholinergic twitch contractions which was reversibly and competitively antagonised by 3-amino-1-nitropropane (50-250 microM). 3-Amino-1-nitropropane (pA2 = 5.0 +/- 0.1) was twice as potent as 2-hydroxysaclofen (pA2 = 4.5 +/- 0.1), but was equipotent with 3-aminopropyl(P-diethoxymethyl)phosphinic acid (CGP 35348) (pA2 = 4.9 +/- 0.2), and did not show any partial agonist activity at these peripheral GABAA or GABAB receptor sites. In rat neocortical slices, 3-amino-1-nitropropane did not activate GABAB receptor sites or affect baclofen-induced suppression of spontaneous discharges. In the cat spinal cord, however, under in vivo conditions, the corresponding nitro analog of baclofen 3-amino-2-(4-chloro)-nitropropane was an agonist at GABAB receptor sites, although more than 60 times weaker than baclofen in depressing monosynaptic excitatory field potentials, whereas 3-amino-1-nitropropane was an extremely weak agonist at bicuculline-sensitive GABAA sites. The differing actions of 3-amino-1-nitropropane at peripheral and central GABAB receptor sites suggest heterogeneity among these receptors.
Ong
J
J
Department of Anaesthesia and Intensive Care, University of Adelaide, Australia.
Kerr
D I
DI
Lacey
G
G
Curtis
D R
DR
Hughes
R
R
Prager
R H
RH
D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002415:Cats; D002540:Cerebral Cortex / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D058785:GABA-A Receptor Agonists; D058788:GABA-B Receptor Antagonists; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008564:Membrane Potentials; D009595:Nitroparaffins / Q000494:pharmacology*; D011407:Propane / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011963:Receptors, GABA-A / Q000378:metabolism; D018080:Receptors, GABA-B / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
D058785:GABA-A Receptor Agonists; D058788:GABA-B Receptor Antagonists; D009595:Nitroparaffins; D011963:Receptors, GABA-A; D018080:Receptors, GABA-B; C035314:1-nitropropane; D005680:gamma-Aminobutyric Acid; D001418:Baclofen; D011407:Propane