Helional induces Ca2+ decrease and serotonin secretion of QGP-1 cells via a PKG-mediated pathway

Abstract

The secretion, motility and transport by intestinal tissues are regulated among others by specialized neuroendocrine cells, the so-called enterochromaffin (EC) cells. These cells detect different luminal stimuli, such as mechanical stimuli, fatty acids, glucose and distinct chemosensory substances. The EC cells react to the changes in their environment through the release of transmitter molecules, most importantly serotonin, to mediate the corresponding physiological response. However, little is known about the molecular targets of the chemical stimuli delivered from consumed food, spices and cosmetics within EC cells. In this study, we evaluated the expression of the olfactory receptor (OR) 2J3 in the human pancreatic EC cell line QGP-1 at the mRNA and protein levels. Using ratiofluorometric Ca2+imaging experiments, we demonstrated that the OR2J3-specific agonist helional induces a transient dose-dependent decrease in the intracellular Ca2+levels. This Ca2+decrease is mediated by protein kinase G (PKG) on the basis that the specific pharmacological inhibition of PKG with Rp-8-pCPT-cGMPS abolished the helional-induced Ca2+response. Furthermore, stimulation of QGP-1 cells with helional caused a dose-dependent release of serotonin that was comparable with the release induced by the application of a direct PKG activator (8-bromo-cGMP). Taken together, our results demonstrate that luminal odorants can be detected by specific ORs in QGP-1 cells and thus cause the directed release of serotonin and a PKG-dependent decrease in intracellular Ca2+.

Development and utilization of human decidualization reporter cell line uncovers new modulators of female fertility

“…Upon binding to extracellular stimuli-including but not limited to odorant molecules, hormones, and transmitters-they transduce the signal internally and activate various signaling pathways in a cell type-dependent manner. In most cell types outside the OE, activation of ORs leads to an increase of intracellular second messenger cAMP and subsequent calcium flux from outside the cells (54)(55)(56)(57)(58)(59)(60)(61). Functions of ORs in non-OE tissues vary as well.…”

Functional expression of olfactory receptors in human primary melanoma and melanoma metastasis

“…The expression of human ORs is not restricted to the olfactory epithelium, but is found in a variety of human tissues . However, the physiological role of these human ORs has only been characterized in a few examples of healthy tissues such as skin and in pathophysiologically altered tissues such as prostate tumor . The few studies investigating the function of ORs in healthy tissues demonstrate that ORs are involved in the secretion processes of cytokines and hormones by airway smooth muscle cells, enterochromaffin cells and keratinocytes; in chemotaxis and acrosome reaction of sperm, the muscle contraction as well as in processes of cell migration and proliferation …”

Odorant Receptor 51E2 Agonist β-ionone Regulates RPE Cell Migration and Proliferation

“…The physiological roles of these ectopically expressed ORs are the subject of ongoing research. The few studies investigating their function show that the activation of human ORs leads to, for example, secretion processes or influences the cell proliferation such as OR51E2 in prostate cancer cells or in melanocytes (Spehr et al, 2003 ; Braun et al, 2007 ; Neuhaus et al, 2009 ; Veitinger et al, 2011 ; Sanz et al, 2014 ; Kang et al, 2015 ; Kim et al, 2015 ; Gelis et al, 2016 ; Kalbe et al, 2016b ; Manteniotis et al, 2016b ; Tsai et al, 2017 ; Weber et al, 2017 ). The various physiological functions depend on the tissue and respective OR.…”