The responsiveness of central benzodiazepine and GABA(A) receptors in vasopressin and spontaneously hypertensive rats.
Administration of diazepam, an agonist of benzodiazepine receptors, and muscimol, an agonist of GABA(A) receptors, resulted in an increase in cytosol GABA-modulin in hypothalamus and cerebellum. Low dose of muscimol, ineffective by itself, completely antagonized the isoniazid, bicuculline and picrotoxin-induced decrease in GABA-modulin activity. In contrast, low dose of diazepam was able to block only the action of isoniazid. That confirms different mechanism of action of muscimol and diazepam. The increase in cytosol GABA-modulin activity in the anterior and posterior hypothalamus of spontaneously hypertensive rats (SHR) and of vasopressin hypertensive rats required much higher doses of muscimol than in normotensive animals showing subsensitivity of GABA(A) receptors in these brain structures. In contrast, the sensitivities of GABA(A) receptors in the cerebellum and of benzodiazepine receptors in the hypothalamus and cerebellum were equal to hypertensive and normotensive rats.
Szmigielska
H
H
Department of Pharmacodynamics, Medical Academy, Lódź, Poland.
Szmigielski
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A
Szadowska
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D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D002352:Carrier Proteins; D003600:Cytosol / Q000378:metabolism; D050485:GABA Plasma Membrane Transport Proteins; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007538:Isoniazid / Q000494:pharmacology; D008236:Lypressin / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009206:Myocardium / Q000201:enzymology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D027361:Organic Anion Transporters; D010761:Phosphorus Radioisotopes; D010852:Picrotoxin / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D051381:Rats; D011918:Rats, Inbred SHR; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*; D014667:Vasopressins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism
D001640:Bicuculline; D002352:Carrier Proteins; D050485:GABA Plasma Membrane Transport Proteins; D007538:Isoniazid; D008236:Lypressin; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D009419:Nerve Tissue Proteins; D027361:Organic Anion Transporters; D010761:Phosphorus Radioisotopes; D010852:Picrotoxin; D047428:Protein Kinase Inhibitors; D011963:Receptors, GABA-A; D014667:Vasopressins; D005680:gamma-Aminobutyric Acid