Noradrenaline release in the rat vena cava is inhibited by gamma-aminobutyric acid via GABAB receptors but not affected by histamine.
1. Segments of the rat vena cava preincubated with [3H]-noradrenaline were superfused with [3H]-noradrenaline-free solution containing desipramine and corticosterone and the effects of gamma-aminobutyric acid (GABA) receptor ligands and of histamine on tritium overflow evoked by transmural electrical stimulation were studied. 2. GABA inhibited, and histamine failed to affect, the electrically (0.66 Hz) evoked tritium overflow both in the absence and presence of rauwolscine (which was present in the superfusion medium in the subsequent experiments). The effect of GABA was less pronounced at a stimulation frequency of 2 Hz. 3. The inhibitory effect of GABA (pIC35 5.83) on the electrically (0.66 Hz) evoked overflow was mimicked by the GABAB receptor agonist, R-(-)-baclofen (6.07) and less potently by S-(+)-baclofen (3.30) and the GABAA receptor agonist, muscimol (3.70). The concentration-response curve of GABA was shifted to the right by the GABAB receptor antagonist, CGP 35348 (P-(3-aminopropyl)-P- diethoxymethyl-phosphinic acid; apparent pA2 4.76), but not affected by the GABAA receptor antagonist, (-)-bicuculline methiodide 100 mumol l-1. Given alone, (-)-bicuculline methiodide slightly increased, and CGP 35348 did not affect, the evoked overflow. 4. The effect of GABA in veins from rats treated for 14 days with RS-baclofen (10 mg kg-1, i.p. once daily) did not differ from that in veins from rats which received the vehicle instead. The effect of GABA also did not differ in veins from rats treated once either with RS-baclofen or with its vehicle. 5. The results suggest that the postganglionic sympathetic nerve fibres in the rat vena cava are endowed with presynaptic GABAB receptors, but not with receptors for histamine. (-)-Bicuculline methiodide increases noradrenaline release by a mechanism not related to GABAA, GABAB, alpha2-receptors or noradrenaline uptake.
Schneider
D
D
Institut für Pharmakologie und Toxikologie, Rheinische Friedrich-Wilhelms-Universität Bonn, Germany.
Schlicker
E
E
Malinowska
B
B
Molderings
G
G
D000818:Animals; D001418:Baclofen / Q000494:pharmacology; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D003345:Corticosterone / Q000494:pharmacology; D003891:Desipramine / Q000494:pharmacology; D004558:Electric Stimulation; D058787:GABA-A Receptor Antagonists; D006632:Histamine / Q000502:physiology*; D066298:In Vitro Techniques; D008297:Male; D009118:Muscimol / Q000494:pharmacology; D009638:Norepinephrine / Q000378:metabolism*; D009943:Organophosphorus Compounds / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology*; D014682:Vena Cava, Inferior / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D058787:GABA-A Receptor Antagonists; D009943:Organophosphorus Compounds; D011963:Receptors, GABA-A; D009118:Muscimol; D015016:Yohimbine; C017069:bicuculline methiodide; D005680:gamma-Aminobutyric Acid; D006632:Histamine; C066430:CGP 35348; D001418:Baclofen; D003891:Desipramine; D003345:Corticosterone; D009638:Norepinephrine; D001640:Bicuculline