当前位置： SCI文献检索 > INTERNATIONAL JOURNAL OF IMMUNOPATHOLOGY AND PHARMACOLOGY期刊下所有文献 > Ritonavir and Saquinavir directly stimulate anterior pituitary prolactin secretion, in vitro.

Ritonavir and Saquinavir directly stimulate anterior pituitary prolactin secretion, in vitro.

Abstract：

:An association between human immunodeficiency virus type I (HIV-1) protease inhibitors (PIs) and galactorrhoea/hyperprolactinemia adverse effect has recently been reported in four HIV-1-infected women treated with PIs (indinavir, nelfinavir, ritonavir or saquinavir). This could be explained by a direct effect of ritonavir and saquinavir on anterior pituitary prolactin (PRL) release, and/or an indirect effect of PIs on the secretion of hypothalamic dopamine, which is the main PRL inhibitory factor. Anterior pituitaries were explanted from adult male Wistar rats, the cells were trypsin dispersed, plated into multiwell cultures and incubated for 1 h with either ritonavir or saquinavir (0.01 nM-1μM). PRL release into the incubation medium was evaluated by radioimmunoassay. Hypothalamic neuronal endings (synaptosomes) were prepared by tissue homogenization, incubated with 3H-dopamine, substituting for the endogenous dopamine pool, and perfused with ritonavir or saquinavir, both basally and during depolarization (K+ 15 mM)-induced dopamine release. Beta-emission from 2 min perfusate fractions, corresponding to 3H-dopamine release, was detected by liquid scintillation scanning. We found that both ritonavir and saquinavir are able to significantly stimulate PRL secretion, with saquinavir slightly more effective than ritonavir. On the contrary, both protease inhibitors do not modify either basal or depolarization-induced dopamine release. We can speculate that HIV PIs despite a high affinity for the catalytic site of HIV protease, could also bind to and inhibit homologous mammalian proteins in the anterior pituitary that are involved in PRL secretion.

journal_name

Int J Immunopathol Pharmacol

journal_title

International journal of immunopathology and pharmacology

authors

Orlando G,Brunetti L,Vacca M

doi

10.1177/039463200201500109

keywords:

subject

Has Abstract

pub_date

2002-01-01 00:00:00

pages

65-68

issue

1

eissn

0394-6320

issn

2058-7384

pii

8

journal_volume

15

pub_type

杂志文章

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