5-CT or DOI augments TRH analog-induced gastric acid secretion at the dorsal vagal complex

Abstract

Serotonin (5-HT) interacts with thyrotropin-releasing hormone (TRH) at the dorsal vagal complex (DVC) to augment TRH-induced stimulation of gastric acid secretion. To investigate the 5-HT receptor family involved in the augmentation response, prototypical 5-HT receptor-selective agonists (146 pmol) were coinjected with the TRH analog RX-77368 (RX; 12 pmol) into the rat DVC in a 30-nl volume. The DVC coordinates were 0.2 mm anterior, 0.2 mm right, 0.6 mm ventral with respect to the calamus scriptorius. Coinjection of RX with the 5-HT agonists 5-carboxyamidotryptamine (5-CT) or (±)-1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI; 5-HT2 agonist) produced a 183 or 103% increase in gastric acid output compared with the RX injection alone. In contrast, coinjection of 2- methyl-5-HT (5-HT3 agonist) with RX produced no effect on RX-induced increase in gastric acid secretion. Moreover, coinjection of SC-53116 (5-HT4agonist) decreased the gastric acid output by 45% compared with the RX response itself. Examination of the RX/5-HT agonist coinjection response in more rostral regions of the DVC using the same doses (5-CT/RX or DOI/RX) revealed that only 5-CT was effective in producing the augmented response to TRH analog. The results suggest that activation of 5-CT- or DOI-sensitive receptors augments, and of 5-HT4 receptors inhibits, the gastric acid response to TRH analog injected into the DVC. Thus the integrated response to several serotonin receptor subtypes may mediate changes to the TRH response induced by 5-HT at the DVC.

Characterization of the in vitro effects of 5‐hydroxytryptamine (5‐HT) on identified neurones of the rat dorsal motor nucleus of the vagus (DMV)

“…To the best of our knowledge, there are no published studies that have investigated the effects on intestinal functions of microinjections of 5‐HT in the DVC. Conversely, several lines of evidence indicate that microinjections of 5‐HT (in combination with TRH) in the DVC affect mainly gastric acid secretion (McTigue et al ., 1992; Krowicki & Hornby, 1995; Yoneda & Tache, 1995; Chi et al ., 1996; Varanasi et al ., 1997). Based on our data reporting a low percentage of DMV gastric‐projecting neurones being affected by 5‐HT, it is tempting to speculate that gastric‐projecting DMV neurones that respond to 5‐HT are indeed the ones involved in gastric‐acid secretion.…”

“…Our conclusions that the excitatory effect of 5‐HT is mediated by 5‐HT 2 receptors corresponds with recent in vitro reports on non‐identified DMV neurones (Albert et al ., 1996) as well as in vivo studies on gastrointestinal function (Yoneda & Tache, 1995; Varanasi et al ., 1997). The inward current induced by 5‐HT via 5‐HT 2 receptors would thus provide a further physiological counterpart to the studies which demonstrated a high level of 5‐HT 2 mRNA in the DMV (Wright et al ., 1995).…”

“…Our data indicating that activation of 5‐HT 1A receptors in NTS decreases the inhibitory GABAergic input onto DMV neurones suggests that the increase in gastric acid secretion observed by Stephens' group upon administration of the 5‐HT 1A receptor agonist 5‐CT (in combination with TRH) might be due to presynaptic disnhiibition (Varanasi et al ., 1997), a possibility we put forth recently (Travagli & Gillis, 1995).…”

“…Vagal preganglionic motoneurones exhibit diverse responses to exogenous application of 5‐HT. For example, 5‐HT acts on gastrointestinal preganglionic neurones to increase gastric acid secretion (McTigue et al ., 1992; Krowicki & Hornby, 1995; Yoneda & Tache, 1995; Chi et al ., 1996; Varanasi et al ., 1997), while 5‐HT, acting through 5‐HT 1A and 5‐HT 1B/1D receptors, exerts opposing effects on bronchoconstrictor preganglionic neurones (Bootle et al ., 1998) whereas cardiac vagal motorneurones are excited by activation of 5‐HT 1A receptors (Sporton et al ., 1991).…”

Roles of 5-HT receptors in the release and action of secretin on pancreatic secretion in rats

“…5-HT is an important neurotransmitter and intercellular messenger to modulate gastrointestinal functions (14). 5-HT stimulates or inhibits gastrointestinal motility (8), alters gastric acid secretion (46), and enhances intestinal secretions (13,56). Immunohistochemical study of gut mucosae (12) has demonstrated that EC cells together with other enteroendocrine cells have a morphological feature consistent with a paracrine action that may play a regulatory role in the release of gut hormones.…”