The Role of Cholecystokinin in Peripheral Taste Signaling in Mice

Abstract

Cholecystokinin (CCK) is a gut hormone released from enteroendocrine cells. CCK functions as an anorexigenic factor by acting on CCK receptors expressed on the vagal afferent nerve and hypothalamus with a synergistic interaction between leptin. In the gut, tastants such as amino acids and bitter compounds stimulate CCK release from enteroendocrine cells via activation of taste transduction pathways. CCK is also expressed in taste buds, suggesting potential roles of CCK in taste signaling in the peripheral taste organ. In the present study, we focused on the function of CCK in the initial responses to taste stimulation. CCK was coexpressed with type II taste cell markers such as Gα-gustducin, phospholipase Cβ2, and transient receptor potential channel M5. Furthermore, a small subset (~30%) of CCK-expressing taste cells expressed a sweet/umami taste receptor component, taste receptor type 1 member 3, in taste buds. Because type II taste cells are sweet, umami or bitter taste cells, the majority of CCK-expressing taste cells may be bitter taste cells. CCK-A and -B receptors were expressed in both taste cells and gustatory neurons. CCK receptor knockout mice showed reduced neural responses to bitter compounds compared with wild-type mice. Consistently, intravenous injection of CCK-Ar antagonist lorglumide selectively suppressed gustatory nerve responses to bitter compounds. Intravenous injection of CCK-8 transiently increased gustatory nerve activities in a dose-dependent manner whereas administration of CCK-8 did not affect activities of bitter-sensitive taste cells. Collectively, CCK may be a functionally important neurotransmitter or neuromodulator to activate bitter nerve fibers in peripheral taste tissues.

Taste sensitivity in anorexia nervosa: A systematic review

“…Moreover, despite evidence that the ability to taste some bitter compounds (e.g., 6‐n‐propylthiouracil, or “PROP”) is genetically determined, no study controlled for the potential of genetic variables, potentially contributing to the heterogeneity of results (Tepper, Banni, Melis, Crnjar, & Tomassini Barbarossa, 2014). Similarly, although a number of hormones, including leptin, cholecystokinin (CCK), and ghrelin, have been implicated in taste sensitivity, the reviewed studies did not assess hormone levels (Cai et al, 2013; Han, Keast, & Roura, 2017; Yoshida et al, 2017). Significantly, these hormones are known to be altered in AN, suggesting that future research could explore the role of these biological factors in taste sensitivity in this population (Atalayer, Gibson, Konopacka, & Geliebter, 2013; Cuntz et al, 2013; Hebebrand, Muller, Holtkamp, & Herpertz‐Dahlmann, 2006).…”

A role for taste receptors in (neuro)endocrinology?

“…The anorexigenic gut hormone CCK is expressed mainly in bitter taste receptor cells of rodents, as well as in a smaller subset of type II cells that express the common subunit of sweet and umami receptors Tas1r3. 36 suggesting that the dominant function of secreted CCK is not autocrine but rather that of a neurotransmitter/neuromodulator. 36 suggesting that the dominant function of secreted CCK is not autocrine but rather that of a neurotransmitter/neuromodulator.…”

“…[33][34][35][36] The corresponding receptors CCK-A and CCK-B are also present in the CCK expressing taste cells, as well as in gustatory neurones. 36 These findings are somewhat contradictory to previous results, which observed changes in sweet taste responses in CCK-A receptor deficient rats indicating the existence of an autocrine feedback loop. 36 These findings are somewhat contradictory to previous results, which observed changes in sweet taste responses in CCK-A receptor deficient rats indicating the existence of an autocrine feedback loop.…”

“…The anorexigenic gut hormone CCK is expressed mainly in bitter taste receptor cells of rodents, as well as in a smaller subset of type II cells that express the common subunit of sweet and umami receptors Tas1r3. [33][34][35][36] The corresponding receptors CCK-A and CCK-B are also present in the CCK expressing taste cells, as well as in gustatory neurones. 36 CCK-receptor knockout mice show selectively reduced bitter responses, whereas sour, salty, sweet and umami responses are unchanged.…”

“…[33][34][35][36] The corresponding receptors CCK-A and CCK-B are also present in the CCK expressing taste cells, as well as in gustatory neurones. 36 CCK-receptor knockout mice show selectively reduced bitter responses, whereas sour, salty, sweet and umami responses are unchanged. Surprisingly, even though CCK-A and -B receptors are expressed in bitter taste receptor cells, bitter responsiveness of bitter taste receptor cells is not affected by CCK, F I G U R E 2 Peptide hormones and hormone receptors expressed in the gustatory system.…”