Characterization and regulation of voltage-operated ca2+ channels in neuroendocrine melanotrope cells of

Contains fulltext : 27463.pdf (publisher's version ) (Open Access)To investigate the way by which multiple incoming neurochemical messengers control second messenger systems to evoke an unambiguous neuronal output, melanotrope neuroendocrine cells in the pars intermedia of the pituitary gland of the South African clawed toad Xenopus laevis were studied. Researches in this thesis reveal: 1) Black-adapted melanotropes express all classes of high-voltage activated (HVA) Ca2+ channels, namely the L, N, P/Q and R types, but no low-voltage-activated (LVA) Ca2+ channels. 2) The N-type and R-type channels are involved in the generation of spontaneous intracellular Ca2+ oscillations. 3) The three GiPCRs inhibit the R-type Ca2+ currents through G / subunits. 4) Activation of the DA-D2 and the NPY-Y1 receptor inhibit the N-type Ca2+ current through another, as yet unidentified mechanism. These receptors inhibit this calcium current with similar strength as they inhibit MSH secretion. 5) Synergy between the two stimulatory neuropeptides TRH and sauvagine reverses D2-receptor-induced inhibition of spontaneous Ca2+ oscillations and action current firing, whereas the individual stimulatory peptides are ineffective. The combination of TRH and sauvagine cannot reverse the D2-receptor-induced inhibition of the R- and N-type Ca2+ currents, and as a result also do not reverse the inhibition of hormone secretion. The results also indicate that the Xenopus melanotrope can generate Ca2+ oscillations that are independent of Ca2+ influx through R- and N-type Ca2+ channels. 6) Ca2+-dependent regulation of Ca2+ currents is correlated with adaptation to background light intensity: in melanotropes from white-adapted toads, Ca2+-dependent regulation of L-type Ca2+ channels is more dominant than in black-adapted melanotropes. 7) In contrast to black-adapted melanotropes, white-adapted melanotropes express LVA Ca2+ channels. In conclusion, the experiments described in this thesis have revealed some important features of the melanotrope cell and have provided new knowledge and better understanding of the mechanisms underlying integration of complex external information by neuroendocrine cells.RU Radboud Universiteit Nijmegen, 4 juli 2006Promotor : Roubos, E.W. Co-promotor : Scheenen, W.J.J.M.144 p