Histidyl-proline-diketopiperazine (cyclo-his-pro) inhibits the suckling- and domperidone-induced transformation of prolactin in the lactating rat.
The histidyl-proline-diketopiperazine (cyclo-his-pro) metabolite of TRH inhibited the transformation of prereleasable PRL within the anterior pituitary and as a consequence, the normal rise in plasma PRL levels when injected before suckling. The dose (400 ng) was administered five times at 1-min intervals. PRL suppression was similar to that resulting from dopamine injected at the same rate. Combined injections of cyclo-his-pro and dopamine, each at the 400 ng/min for 5 min rate, provoked a greater inhibition of PRL than did either alone. Neither cyclo-his-pro nor dopamine inhibited the suckling-induced release of PRL in rats whose PRL had previously been transformed by a short (10-min) period of suckling. The stimulatory effects of iv administered domperidone (0.005 or 0.01 mg/rat) and haloperidol (0.2 mg/rat) upon PRL transformation and release in the lactating rat were substantially reduced by cyclo-his-pro in a dose-related fashion over a range of doses from 200-800 ng/min for 5 min. These results demonstrate that cyclo-his-pro inhibits PRL secretion in the lactating rat after suckling, primarily through inhibition of the transformation phase, and that the inhibitory mechanism may involve an interaction with dopamine.
D000818:Animals; D004294:Domperidone / Q000037:antagonists & inhibitors*; D004298:Dopamine / Q000494:pharmacology; D005260:Female; D007774:Lactation; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000378:metabolism; D011247:Pregnancy; D011388:Prolactin / Q000378:metabolism*; D051381:Rats; D012636:Secretory Rate; D013391:Sucking Behavior / Q000502:physiology*
D010456:Peptides, Cyclic; D010879:Piperazines; D004294:Domperidone; D011388:Prolactin; C015924:histidyl-proline diketopiperazine; D004298:Dopamine