The in vitro regulation of growth hormone secretion by orexins

被引:24
作者
Chen, C
Xu, RW
机构
[1] Monash Univ, Prince Henrys Inst Med Res, Clayton, Vic 3168, Australia
[2] Monash Univ, Dept Physiol, Clayton, Vic 3168, Australia
基金
英国医学研究理事会;
关键词
orexin; GH; Ca2+ currents; GHRH; PKC;
D O I
10.1385/ENDO:22:1:57
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Orexins, orexigenic neuropeptides, have recently been discovered in lateral hypothalamus and play an important role in the regulation of pituitary hormone secretion. Two subtypes of orexin receptors (orexin-1 and orexin-2) have been demonstrated in pituitaries. In this experiment, the effects of orexins on voltage-gated Ca2+ currents and the GH release in primary cultured ovine somatotropes were examined. Voltage-gated Ca2+ currents were isolated in ovine somatotropes as L, T, and N currents using whole-cell patch-clamp techniques and specific Ca2+ channel blocker and toxin. Application of orexin-A or orexin-B (100 nM) significantly, dose-depen-dently, and reversibly increased only nifedipine-sensitive L-type Ca2+ current. Inhibitors of PKC (calphostin C, PKC inhibitory peptide) but not inhibitors of PKA (H89, PKA inhibitory peptide) cancelled the increase in the L current by orexins. Co-administration of orexin-A and GHRH (10 nM) showed an additive effect on the L current. Specific intracellular Ca2+-store-depleting reagent, thapsigargin (1 muM) did not affect the orexin-induced increase in the L current. Orexin-B alone slightly increased GH release and co-administration of orexin-A and GHRH synergistically stimulated GH secretion in vitro. It is therefore suggested that orexins may play an important role in regulating GHRH-stimulated GH secretion through an increase in the L-type Ca2+ current and the PKC-mediated signaling pathways in ovine somatotropes.
引用
收藏
页码:57 / 66
页数:10
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