INHIBITION OF CA2+-INDUCED CALCITONIN SECRETION BY SOMATOSTATIN - ROLES OF VOLTAGE DEPENDENT CA2+ CHANNELS AND G-PROTEINS

被引:18
作者
SCHERUBL, H [1 ]
HESCHELER, J [1 ]
SCHULTZ, G [1 ]
KLIEMANN, D [1 ]
ZINK, A [1 ]
ZIEGLER, R [1 ]
RAUE, F [1 ]
机构
[1] UNIV HEIDELBERG,INNERE MED 1 ENDOKRINOL & STOFFWECHSEL ABT,W-6900 HEIDELBERG,GERMANY
关键词
CALCITONIN SECRETION; CYTOSOLIC CALCIUM; CALCIUM CHANNELS; SOMATOSTATIN; G-PROTEINS; PERTUSSIS TOXIN MEDULLARY THYROID CARCINOMA; RAT CELL LINE RMTC-44-2;
D O I
10.1016/0898-6568(92)90009-W
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Somatostatin has recently been applied therapeutically for hypercalcitonemia in patients with calcitonin-producing tumours. Using calcitonin-secreting cells (C-cells) of the medullary thyroid carcinoma cell line rMTC 44-2, we investigated the inhibitory action of somatostatin on calcitonin release, cytosolic Ca2+ and Ca2+ channel currents. The Ca2+-induced rises of the cytosolic Ca2+ and calcitonin secretion were greatly inhibited by somatostatin or its stable analogue octreotide. The effects of somatostatin were pertussis toxin-sensitive. Under voltage clamp conditions, C-cells exhibited slowly inactivating Ca2+ channel currents. Bath application of 100 nM somatostatin reversibly reduced the Ca2+ channel current by about 30%. The Ca2+ channel current and its inhibition by somatostatin were not affected by intracellularly applied cyclic AMP. Moreover, pretreating the cells with pertussis toxin had no effect on the control Ca2+ channel currents but greatly abolished its inhibition by somatostatin. The data show that somatostatin suppresses the Ca2+-stimulated calcitonin secretion by inhibiting voltage-dependent Ca2+ channel currents and by lowering cytosolic Ca2+. These actions of somatostatin involve pertussis toxin-sensitive G-proteins and occur independently of changes in the cyclic AMP concentration.
引用
收藏
页码:77 / 85
页数:9
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