Endogenous GABA acts on GABAB receptors in nucleus tractus solitarius to increase blood pressure.
Previous studies found that injection of the GABA uptake inhibitor nipecotic acid into the nucleus tractus solitarius (NTS) increases arterial pressure. This effect of nipecotic acid was not antagonized by the selective GABAA receptor blocking agent bicuculline, suggesting that the action of nipecotic acid was mediated through an action of GABA on GABAB receptors in the NTS. The present studies examined this issue using a newly described GABAB antagonist, phaclofen. Injection of phaclofen (4 nmol in 100 nl artificial CSF) into the NTS of chloralose-anesthetized rats produced a slight decrease in arterial pressure (-8 +/- 2 mmHg) lasting less than 1 min. Smaller doses had no effect. Phaclofen antagonized in a dose-dependent (0.5-4 nmol) manner the increase in arterial pressure produced by injection into the NTS of the GABAB agonist baclofen (5-100 pmol). In contrast, phaclofen had no effect on the pressor response elicited by injection into the NTS of the GABAA agonist muscimol. Phaclofen (4 nmol) injected into the NTS totally reversed the increase in blood pressure elicited by injection into the NTS of a maximally effective dose of nipecotic acid (10 nmol). Phaclofen also inhibited the pressor response elicited by injection into the NTS of another indirectly acting GABA agonist, gamma-vinylGABA (GVG). Although GVG is an effective inhibitor of GABA transaminase, the enzyme involved in the metabolism of GABA, the time course of inhibition of GABA transaminase evoked by GVG was not consistent with the pressor response being produced by this mechanism. However, the pressor response elicited by GVG is consistent with its reported ability to inhibit GABA uptake.(ABSTRACT TRUNCATED AT 250 WORDS)
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AF
Department of Behavioral Neuroscience, University of Pittsburgh, PA 15260.
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JC
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000614:Aminocaproates / Q000494:pharmacology; D000818:Animals; D001418:Baclofen / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D008297:Male; D008526:Medulla Oblongata / Q000502:physiology*; D009118:Muscimol / Q000494:pharmacology; D009557:Nipecotic Acids / Q000037:antagonists & inhibitors; D011392:Proline / Q000031:analogs & derivatives*; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000502:physiology*; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000502:physiology*
D000614:Aminocaproates; D018756:GABA Antagonists; D058787:GABA-A Receptor Antagonists; D009557:Nipecotic Acids; D011963:Receptors, GABA-A; C052329:phaclofen; C030278:nipecotic acid; D009118:Muscimol; D005680:gamma-Aminobutyric Acid; D011392:Proline; C010983:homoproline; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin; D001418:Baclofen