Plasticity of adrenoceptor responsiveness on iranp secretion and pro-anp mrna expression in hypothalamic neuron cultures: Modulation by dexamethasone

Weiqing Huang, Dan Lee, Zhiyu Yang, David L. Copolov, Alan T. Lim

Research output: Contribution to journalArticleResearchpeer-review

14 Citations (Scopus)

Abstract

Atrial Natriuretic Peptide (ANP) or its smaller congeners are produced and secreted from the rat hypothalamus. Whereas immunoreactive (ir)ANP secretion and proANP mRNA expression in hypothalamic cell cultures of neonatal rats were augmented by norepinephrine acting through its α2-adrenoceptors (AR), in the perifusion studies of adult hypothalamic fragments β-AR was involved in the upregulation of irANP release. Here, we report that dexamethasone (DM) modulates irANP secretion and pro-ANP mRNA expression from hypothalamic neurons in culture by switching the adrenoceptor responsiveness of the cells from α2- to that of β-AR. In long term cultures of hypothalamic cells, treatment with clonidine (α2-AR agonist) increased irANP secretion in a dose related manner. This effect of clonidine was abolished by DM, a glucocorticoid which by itself had little effect on the basal release of irANP. In contrast, isoprenaline, a β-AR agonist which was ineffective when applied alone, enhanced irANP secretion from hypothalamic cultures in the presence of DM. Concurrent incubation of DM (5 nM) and isoprenaline (10 μM) augmented irANP release approximately 3 fold above that of cultures treated with DM alone (22.6 ± 2.2; mean ± se, n = 4). However, phenylephrine, an ctpAR agonist alone or in the presence of DM failed to stimulate irANP release. These immunoassay findings were accompanied by corresponding changes in the abundance of pro-ANP mRNA in the cultures as examined by colorimetric Northern blot analysis employing a 30 mer oligonucleotide probe corresponding to the first 10 amino acid sequence of rANP1-28. We conclude from the above observations that glucocorticoids modulate irANP secretion and pro-ANP mRNA expression in hypothalamic neurons by altering the responsiveness of the cells horn α2-AR to that of β-AR.

Original languageEnglish
Pages (from-to)1562-1564
Number of pages3
JournalEndocrinology
Volume131
Issue number3
DOIs
Publication statusPublished - 1 Jan 1992
Externally publishedYes

Cite this