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Serotonergic signalling between thyroid cells: Protein kinase C and 5‐HT 2 receptors in the secretion and action of serotonin
Author(s) -
Tamir Hadassah,
Hsiung ShuChi,
Yu PeiYing Y.,
Liu KuoPeing,
Adlersberg Mella,
Nunez Eladio A.,
Gershon Michael D.
Publication year - 1992
Publication title -
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Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.890120209
Subject(s) - endocrinology , medicine , protein kinase c , receptor , biology , secretion , calcium in biology , chemistry , microbiology and biotechnology , signal transduction
Parafollicular (PF) cells of the thyroid gland are neural crest derivatives, which costore the neurotransmitter, 5‐hydroxytryptamine (5‐HT) with calcitonin. PF cells are located adjacent to follicular (F) cells within the basement membrane of thyroid follicles. It has been proposed that 5‐HT serves an intercellular signalling function in the thyroid and that F cells are its target. This proposal was tested by using cell lines derived from PF (medullary thyroid carcinoma [MTC]) and F (FRTL‐5) cells to study the mechanisms that mediate the secretion and action of 5‐HT. Secretion of 5‐HT by MTC cells was evoked by thyroid stimulating hormone, thyrotropin (TSH), elevated extracellular calcium (↑[Ca 2+ ] e ), or by agents that increase intracellular cAMP (↑[cAMP] i ). When protein kinase C (PKC) was down‐regulated by prolonged treatment of MTC cells with phorbol 12‐myristate 13‐acetate (PMA), or PKC was inhibited by staurosporin, the TSH‐or PMA‐evoked secretion of 5‐HT was blocked; however, interference with PKC function did not affect 5‐HT secretion evoked by ↑ [Ca 2+ ] e or ↑ [cAMP] i . In the putative targets, FRTL‐5 cells, 5‐HT increased the turnover of phosphoinositides (PI), cytosolic calcium (↑[Ca 2+ ] i ), ↑[cAMP] i , and biphasically modified the effect of TSH on cAMP. All of these 5‐HT effects were inhibited by 5‐HT 2 receptor antagonists (spiperone and ketanserin) and by pertussis toxin (PTx), suggesting that the actions of 5‐HT are mediated by 5‐HT 2 receptors, which are coupled to a G protein. This suggestion was supported by the following additional observations: FRTL‐5 membranes bound the 5‐HT 2 agonist, [ 125 I]2,5‐dimethoxy‐4‐iodophenylisopropylamine ([ 125 I]‐DOI), and anti‐idiotypic anti‐bodies, which recognize 5‐HT 2 receptors. [ 125 I]‐DOI binding was inhibited by guanosine‐5′‐O‐(3‐thiotriphosphate) (GTP‐γ‐S) and the antibodies were displaced by spiperone. Data are consistent with the hypothesis that 5‐HT serves as a PF to F cell messenger. © 1992 Wiley‐Liss, Inc.