The intrinsic activity of (-)-3-PPP (preclamol) on pituitary DA receptors in female rats is enhanced following chronic DA depletion.
The present investigation was aimed at comparing the influence of the partial dopamine (DA) receptor agonist (-)-3-PPP (preclamol) on prolactin release in acutely hyperprolactinemic but otherwise intact female rats and female rats subjected to chronic DA depletion. One group of animals received daily vehicle injections (controls) and another group daily reserpine (1 mg/kg) injections for a period of seven days. On the eighth day all animals were administered 10 mg/kg of reserpine in order to eliminate endogenous DA and elevate serum prolactin levels. In the control group (-)-3-PPP lowered serum prolactin levels only moderately. In contrast, in the chronically reserpinized female rats, a pronounced reduction of prolactin secretion was observed. It is suggested that this increase in intrinsic activity of (-)-3-PPP following chronic DA depletion reflects an enhanced responsiveness of hypophyseal DA receptors, possibly due to conformational changes in the receptor molecules. Our observations lend further support to the hypothesis that an inverse relationship exists between the intrinsic activity of a mixed agonist/antagonist and the degree of previous receptor occupancy.
Carlsson
M
M
Department of Pharmacology, University of Göteborg, Sweden.
Eriksson
E
E
D000818:Animals; D004298:Dopamine / Q000172:deficiency*; D005260:Female; D006966:Hyperprolactinemia / Q000139:chemically induced / Q000503:physiopathology; D010880:Piperidines / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011954:Receptors, Dopamine / Q000187:drug effects / Q000502:physiology*; D012110:Reserpine
D010880:Piperidines; D011954:Receptors, Dopamine; D012110:Reserpine; D011388:Prolactin; C026539:preclamol; D004298:Dopamine