Lack of effect of histidyl-proline diketopiperazine on basal level and TRH-induced response of cytosolic calcium concentration in rat lactotrophs.
Histidyl-proline diketopiperazine [cyclo(His-Pro)] has recently been shown to inhibit prolactin (PRL) secretion in vitro and in vivo. This peptide is well known as a metabolite of thyrotropin-releasing hormone (TRH), which is one of the endogenous secretagogues of PRL. In this study, we investigated the effect of cyclo (His-Pro) on the cytosolic Ca2+ concentration [[Ca2+]i) in cultured lactotrophs by using a lactotroph-enriched fraction separated from female rat pituicytes by centrifugal elutriation. TRH (10 nM) induced a rapid rise in [Ca2+]i in the lactotrophs, followed by a plateau phase of prolonged increase in [Ca2+]i. In contrast, the addition of 100 microM of cyclo (His-Pro) caused no changes in the basal level or the TRH-induced plateau response of [Ca2+]i. Although pretreatment with cyclo (His-Pro) tended to decrease the biphasic increase in [Ca2+]i induced by TRH, the inhibitory effect was not statistically significant. These results demonstrated that cyclo (His-Pro) has no effect on [Ca2+]i in lactotrophs, and does not affect the TRH-induced increase in [Ca2+]i, indicating that the inhibition of PRL secretion by cyclo (His-Pro) may be primarily mediated by other intracellular messengers such as cyclic nucleotides and secondarily involved in other inhibitory systems including that of dopamine.
Yamada
M
M
First Department of Internal Medicine, Gunma University School of Medicine, Maebashi, Japan.
Izumi
S
S
Makino
T
T
Mori
M
M
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002498:Centrifugation; D003600:Cytosol / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D016257:Fura-2; D010456:Peptides, Cyclic / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D010903:Pituitary Gland, Anterior / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*
D010456:Peptides, Cyclic; D010879:Piperazines; D013973:Thyrotropin-Releasing Hormone; C015924:histidyl-proline diketopiperazine; D002118:Calcium; D016257:Fura-2