Cimetidine-induced prolactin release: possible involvement of the GABA-ergic system.
The mechanism of cimetidine-induced prolactin (PRL) release was studied. Intracarotid (i.a.) administration of 1 mg/kg of impromidine, the most specific H2 histamine agonist known, did not counteract the cimetidine-induced hypersecretion of PRL. Pre-treatment with benzodiazepines (diazepam or lorazepam, 3 mg/kg/i.a.) completely suppressed it. Administration of gamma-aminobutyric acid (GABA 5 mg/kg/i.a.) was also able to prevent it, but to a lesser extent than benzodiazepines. Simultaneous administration of doses of diazepam (1.5 mg/kg/i.a.) and GABA (3 mg/kg/i.a.) ineffective per se markedly blunted the increase of PRL by cimetidine. We conclude that cimetidine does not induce hypersecretion of PRL by its action on histamine H2 receptors, but through other pharmacological activities of the drug, such as perhaps interaction with the GABA-ergic system in the pituitary.
Sibilia
V
V
Netti
C
C
Guidobono
F
F
Pagani
F
F
Pecile
A
A
D000818:Animals; D002927:Cimetidine / Q000494:pharmacology*; D003975:Diazepam / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D017446:Impromidine; D008297:Male; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011969:Receptors, Histamine H1 / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology / Q000502:physiology*
D007093:Imidazoles; D011969:Receptors, Histamine H1; D005680:gamma-Aminobutyric Acid; D002927:Cimetidine; D011388:Prolactin; D017446:Impromidine; D003975:Diazepam