Effect of THIP and SL 76002, two clinically experimented GABA-mimetic compounds, on anterior pituitary GABA receptors and prolactin secretion in the rat

Journal Article · Mon Mar 02 04:00:00 EST 1987 · Life Sci.; (United States)

DOI:https://doi.org/10.1016/0024-3205(87)90036-1· OSTI ID:6803172

Apud, J A; Masotto, C; Racagni, G

In the present study, the ability of three direct GABA agonists, muscimol, THIP and SL 76002 to displace /sup 3/H-GABA binding from anterior pituitary and medio-basal hypothalamus membranes was evaluated. Further, the effect of both THIP and SL 76002 on baseline prolactin levels or after stimulation of hormone release with haloperidol has been also studied. Either muscimol, THIP or SL 76002 have shown to posses 7-, 7- and 3-fold higher affinity, respectively, for the central nervous system than for the anterior pituitary /sup 3/H-GABA binding sites. Moreover, THIP and SL 76002 have demonstrated to be respectively, 25- and 1000- fold less potent than muscimol in inhibiting /sup 3/H- GABA binding at the level of the anterior pituitary and about 25- and 2700-fold less potent at the level of the medio-basal hypothalamus. Under basal conditions, either THIP or SL 76002 were ineffective to reduce prolactin release. However, after stimulation of prolactin secretion through blockade of the dopaminergic neurotransmission with haloperidol (0.1 mg/kg), both THIP (10 mg/kg) and SL 76002 (200 mg/kg) significantly counteracted the neuroleptic-induced prolactin rise with a potency which is in line with their ability to inhibit /sup 3/H-GABA binding in the anterior pituitary. The present results indicate that both compounds inhibit prolactin release under specific experimental situations probably through a GABAergic mechanism. In view of the endocrine effects of these GABA-mimetic compounds, the possibility arises for an application of these type of drugs in clinical neuroendocrinology. 35 references, 3 figures, 2 tables.

• Research Organization: Univ. of Milan, Italy
• OSTI ID: 6803172
• Journal Information: Life Sci.; (United States), Journal Name: Life Sci.; (United States) Vol. 40:9; ISSN LIFSA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
AFFINITY
ANIMALS
ANTIHYPERTENSIVE AGENTS
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CARDIOVASCULAR AGENTS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
DRUGS
ENDOCRINE GLANDS
GLANDS
GONADOTROPINS
HORMONES
ISOTOPE APPLICATIONS
KINETICS
LABELLED COMPOUNDS
LTH
MAMMALS
MEMBRANE PROTEINS
MEMBRANES
NERVOUS SYSTEM
ORGANIC COMPOUNDS
ORGANS
PEPTIDE HORMONES
PITUITARY GLAND
PITUITARY HORMONES
PROTEINS
RATS
REACTION KINETICS
RECEPTORS
RODENTS
SECRETION
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES