Pressor responses to central injection of H2 antagonists not caused by GABA blockade.
In awake rats, ranitidine was more effective than cimetidine in elevating blood pressure following intracerebroventricular (i.c.v.) injection, yet neither drug affected the hypotensive response to subsequent injections of muscimol (8.8 nmol i.c.v.). Bicuculline (0.01 nmol) microinjected into the inferior colliculus of rats caused clonic seizures whereas cimetidine (100 nmol) had no effect. The antihistamines did not prevent GABAB receptor-mediated inhibition of twitch responses in transmurally stimulated guinea-pig ileum. Ranitidine potentiated rather than inhibited GABAA receptor-mediated contractions of ileum longitudinal muscle. Cimetidine had no effect on these responses except at high concentrations (3 X 10(-4) M) which caused a slight dextral shift in the contractile response curve for GABA that may be attributed to antimuscarinic actions of cimetidine. Taken together, these data do not support the concept that the centrally mediated pressor effects of H2 antagonists are caused by GABA receptor blockade.
Trzeciakowski
J P
JP
Frye
G D
GD
D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects*; D002927:Cimetidine / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D006168:Guinea Pigs; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D007082:Ileum / Q000187:drug effects; D066298:In Vitro Techniques; D007245:Inferior Colliculi; D008297:Male; D008845:Microinjections; D009118:Muscimol / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009197:Myenteric Plexus / Q000502:physiology; D011899:Ranitidine / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D011963:Receptors, GABA-A / Q000187:drug effects*
D006635:Histamine H2 Antagonists; D011963:Receptors, GABA-A; D009118:Muscimol; D002927:Cimetidine; D011899:Ranitidine; D001640:Bicuculline