Bombesin microinjected into the dorsal vagal complex inhibits TRH-stimulated gastric contractility in rats

The effects of centrally injected bombesin on central and peripheral stimulated gastric contractility were investigated in fasted urethane-anesthetized rats. Miniature strain gauge force transducers were acutely implanted on the corpus of the stomach and gastric contractility was analyzed by computer. Intracisternal injection of the stable thyrotropin-releasing hormone (TRH)-analog RX 77368 (77 pmol) induced a stimulation of gastric contractility for 40 min. Intracisternal injection of bombesin (62-620 pmol) followed 30 min later by that of RX 77368 resulted in a dose-related inhibition of the TRH-analog-induced gastric contractility. Intracisternal injection of bombesin (620 pmol) did not modify gastric contractility stimulated by intravenous carbachol. Stimulation of gastric contractility induced by TRH-analog microinjected into the dorsal vagal complex (DVC) was dose-related suppressed by concomitant injections of bombesin (6.2-620 pmol). Neither bombesin alone (6.2 pmol) nor vehicle modified basal gastric contractility. These results demonstrate that bombesin acts within the brain to inhibit vagally stimulated gastric contractility and that the DVC is a sensitive site for bombesin inhibitory action. These findings suggest a possible interaction between TRH and bombesin in the central vagal regulation of gastric contractility.     

Microinjection of thyrotropin-releasing hormone analogue into the central nucleus of the amygdala stimulates gastric contractility in rats

The effect on gastric contractility following bilateral microinjection of thyrotropin-releasing hormone (TRH) analog. RX 77368, into the central nucleus of the amygdala was examined in fasted. urethane-anesthetized rats. Extraluminal force transducers were used to measure gastric corpus contractility. Bilateral microinjection of RX 77368 (0.5 μg. 1.0 μg,n = 6 each) stimulated gastric contractility for up to 120 min post-injection,P < 0.05. Gastric contractility was not significantly stimulated by microinjection of 0.1 μg RX 77368. 0.1% bovine serum albumin (BSA) into the central nucleus or RX 77368 (0.5 μg. 1.0 μg) into sites adjacent to the central nucleus. Peak responses (1.0 μg) occurred 40 min post-injection and represented a 16-26-fold increase over basal values. The frequency of gastric contraction waves was attenuated for 0–90 min in rats receiving central amygdaloid microinjection of RX 77368 (0.1. 0.5 or 1.0 μg) versus rats microinjected with the vehicle or RX 77368 into sites adjacent to the central nuclei. The stimulatory effect of RX 77368 (1.0 μg) on gastric contractility was abolished by subdiaphragmatic vagotomy. These results indicate that the TRH analog. RX 77368, acts within the central amygdala to vagally stimulate gastric contractility.     

Microinjection of TRH analogs into the raphe pallidus stimulates gastric acid secretion in the rat

The effects of microinjection of the stable thyrotropin-releasing hormone (TRH) analog, RX 77368, [pGlu-His-(3,3'-dimethyl)-Pro-NH2] into the raphe pallidus on gastric acid secretion were studied in urethane-anesthetized rats with gastric fistula. RX 77368 microinjected into the raphe pallidus at doses of 0.07, 0.7 and 7.7 pmol induced a dose-dependent net stimulation of gastric acid secretion (7 +/- 4, 50 +/- 7 and 61 +/- 12 mumol/h respectively). The peak acid response was reached within 30 min and returned to basal level 90 min post-injection. The stimulatory effect was abolished by bilateral cervical vagotomy and pirenzepine pretreatment (1 mg/kg, i.v.). RX 77368 (7.7 pmol) microinjected into the inferior olive or pyramidal tract induced smaller or no gastric acid secretory response. These results demonstrate that chemical stimulation of the raphe pallidus increases gastric acid secretion through vagal pathways and peripheral muscarinic receptors. These data suggest that the nucleus raphe pallidus may be involved in vagal modulation of gastric acid secretion in the rat.     

Raphe pallidus stimulation increases gastric contractility via TRH projections to the dorsal vagal complex in rats

The role of thyrotropin releasing hormone (TRH) in the dorsal vagal complex (DVC) in mediating the enhanced gastric contractility induced by glutamate (100 pmol) microinjected into the raphe pallidus (Rpa) was investigated in urethane-anesthetized rats acutely implanted with miniature strain gauge force transducers on the corpus of the stomach. Glutamate-induced stimulation of gastric contractility was dose-dependently inhibited by bilateral microinjection into the DVC of TRH antibody (0.17, 0.85 or 1.7 μg/100 nl/site) but not by vehicle. TRH antibody microinjected into the dorsal medullary reticular field had no effect. These data indicate that activation of Rpa neurons by glutamate increases gastric motor function through TRH release in the DVC.     

TRH stimulation and L-glutamic acid inhibition of proximal gastric motor activity in the rat dorsal vagal complex

The importance of the dorsal vagal complex (DVC) in the control of gastric motor activity has been previously established by electrical and chemical stimulation of this region. We have further evaluated excitatory and inhibitory influences on motor activity of the gastric corpus by microinjection of L-glutamic acid (GLU) and thyrotropin-releasing hormone (TRH) into the DVC. GLU and TRH were ejected by pressure (20-30 psi) in 1-10 nl vol. from multibarreled micropipettes and intraluminal pressure in the gastric corpus was measured using a manometric catheter placed into the stomach through the pylorus of urethane-chloralose anesthetized rats. Gastric motor activity was monitored while micropipettes were advanced from the surface of the dorsomedial medulla to a depth of 1 mm in 100 micron increments. Microinjections of GLU (1-10 pmol) at depths of 200-600 microns below the surface of the brainstem caused a decrease in tonic intraluminal pressure and amplitude of phasic contractions of the gastric corpus. Injection of TRH (1-10 pmol) at depths of 200-800 microns increased both tonic intraluminal pressure and amplitude of phasic contractions. The responses to GLU (10 pmol) and TRH (10 pmol) were abolished by hexamethonium and vagotomy; atropine abolished the effect of TRH and attenuated that of GLU. It is concluded that GLU evokes only vagally mediated inhibitory effects on tonic and phasic gastric motor activity when microinjected into the DVC. In contrast, injection of TRH at the same loci causes only vagal cholinergic increases in motor activity. Subpopulations of neurons in the DVC may, therefore, be activated by specific neurotransmitters having opposite effects on gastric motor activity.     

TRH stimulation andl-glutamic acid inhibition of proximal gastric motor activity in the rat dorsal vagal complex

The importance of the dorsal vagal complex (DVC) in the control of gastric motor activity has been previously established by electrical and chemical stimulation of this region. We have further evaluated excitatory and inhibitory influences on motor activity of the gastric corpus by microinjection ofl-glutamic acid (GLU) and thyrotropin-releasing hormone (TRH) into the DVC. GLU and TRH were ejected by pressure (20–30 psi) in 1–10 nl vol. from multibarreled micropipettes and intraluminal pressure and the gastric corpus was measured using a manometric catheter placed into the stomach through the pylorus of urethane-chloralose anesthetized rats. Gastric motor activity was monitored while micropipettes were advanced from the surface of the dorsomedial medulla to a depth of 1 mm in 100 μm increments. Microinjections of GLU (1–10 pmol) at depths of 200–600 μm below the surface of the brainstem caused a decrease in tonic intraluminal pressure and amplitude of phasic contactions of the gastric corpus. Injection of TRH (1–10 pmol) at depths of 200–800 μm increased both tonic intraluminal pressure and amplitude of phasic contractions. The responses to GLU (10 pmol) and TRH (10 pmol) were abolished by hexamethonium and vagotomy; atropine abolished the effect of TRH and attenuated that of GLU. It is concluded that GLU evokes only vagally mediated inhibitory effects on tonic and phasic gastric motor activity when microinjected into the DVC. In contrast, injection of TRH at the same loci causes only vagal cholinergic increases in motor activity. Subpopulations of neurons in the DVC may, therefore, be activated by specific neurotransmitters having opposite effects on gastric motor activity.     

Excitatory stimulation of neurons in the arcuate nucleus initiates central CRF-dependent stimulation of colonic propulsion in rats

It is well established that autonomic control of digestive function is modulated by central autonomic neurotransmission. In this context it has been shown that digestive function can be modulated by exogenous neuropeptides microinjected into specific brain sides. Furthermore, there is considerable evidence suggesting that neurons projecting from the arcuate nucleus (ARC) to the PVN may be the source of endogenous neuropeptide release in the PVN. Neuronal projections from the ARC have been proposed to target corticotropin-releasing factor (CRF)-positive neurons in the PVN. Exogenous CRF in the PVN has been shown to modulate digestive function like gastric acid secretion and GI motility. Recently we have demonstrated that activation of ARC neurons inhibits gastric acid secretion via central CRF receptor dependent mechanisms. This poses the question whether neuronal activation of the ARC alters digestive function beside gastric acid secretion. In the present study we investigated whether CRF pathways in the ARC-PVN axis are involved in the modulation of colonic motility. First we examined the effect of an excitatory amino acid, kainate, microinjected into the ARC on colonic motility in anesthetized rats. Colonic motility was measured with a non-absorbable radioactive marker using the geometric center method. Kainate (120 pmol/rat) bilaterally microinjected into the ARC induced a significant stimulation of colonic propulsion. To assess the contribution of hypothalamic CRF to the effects of neuronal stimulation in the ARC on colonic motility we performed consecutive bilateral microinjections of an antagonist to CRF receptors into the PVN and the excitatory amino acid kainate into the ARC. Microinjection of the non-selective CRF receptor antagonist, astressin (100 ng), into the PVN abolished the stimulatory effect of neuronal activation in the ARC by kainate on colonic motor function. The data indicate that activation of neurons in the ARC stimulates colonic motility via CRF-receptor-mediated mechanism in the PVN and underlines the important role of the ARC-PVN circuit for the integrative CNS regulation of GI function.     

Microinjection of thyrotropin-releasing hormone in the paraventricular nucleus of the hypothalamus stimulates gastric contractility

Changes in gastric contractility following microinjection of thyrotropin-releasing hormone (TRH) into the paraventricular nucleus of the hypothalamus (PVN) were examined in fasted, urethane-anesthetized rats. Gastric contractility was measured with extraluminal force transducers and analysed by computer. Unilateral and bilateral PVN microinjections of TRH (0.5 and 1.0 μg) significantly increased the force index of gastric contractions from 0 to 60 min postinjection, when compared with animals microinjected with 0.1 μg TRH, 0.1% BSA or TRH (0.5 and 1.0 μg TRH) in sites adjacent to the PVN. The gastric force index was also significantly elevated from 61 to 120 min postinjection in rats receiving bilateral PVN microinjections of TRH (0.5 and 1.0 μg). Peak gastric responses occurred within 10–20 min postinjection and represented an approximately eight-fold increase over basal values. In the remaining groups, the force index was not significantly altered from preinjection values. The excitatory action of TRH (1.0 μg) on gastric contractility was completely abolished by subdiaphragmatic vagotomy. These results suggest that TRH acts within the PVN to stimulate gastric contractility via vagal-dependent pathways.     

Ghrelin-induced stimulation of colonic propulsion is dependent on hypothalamic neuropeptide Y1- and corticotrophin-releasing factor 1 receptor activation

Peptides participating in the hypothalamic control of feeding behaviour are also involved in the central autonomic control of gastrointestinal functions, such as secretion and motility. An anatomical interaction and functional relationship in the central nervous system between the feeding-related peptides neuropeptide Y and ghrelin is well documented. Furthermore, it has been shown that feeding-related peptides can influence digestive function via central corticotrophin-releasing factor (CRF) pathways. In the present study, we investigated the role of ghrelin in the central autonomic control of colonic motility. Furthermore, we addressed the hypothesis that ghrelin is involved in the hypothalamic control of colonic motor function, utilizing central neuropeptide Y receptors and hypothalamic CRF pathways. Ghrelin (0.03, 0.06 and 0.12 nmol) bilaterally microinjected into the paraventricular nucleus (PVN) induced a significant stimulation of colonic propulsion. In particular, the colonic transit time decreased from 312+/-7 min to 198+/-12 min. Microinjection of the neuropeptide Y1 receptor antagonist, BIBP-3226 (200 pmol), or the nonselective CRF receptor antagonist, astressin (30 pmol), into the PVN abolished the stimulatory effect of ghrelin injected into the PVN on colonic transit time, whereas pretreatment with the selective CRF2 receptor, antisauvagine-30 (28 pmol), failed to affect the effect of PVN-ghrelin injection on colonic propulsion. These results suggest that ghrelin can act as central modulator of gastrointestinal motor functions at the level of the PVN via neuropeptide Y1- and CRF1 receptor-dependent mechanisms.     

Excitatory stimulation of neurons in the arcuate nucleus inhibits gastric acid secretion via vagal pathways in anesthetized rats

It is well established that autonomic control of gastrointestinal function is modulated by central autonomic neurotransmission. In this context it has been shown that gastrointestinal motility and secretion can be modulated by exogenous neuropeptides microinjected into the paraventricular nucleus of the hypothalamus (PVN). Furthermore, there is considerable evidence suggesting that neurons projecting from the arcuate nucleus (Arc) to the PVN may be the source of endogenous neuropeptide release in the PVN. This poses the question whether stimulation of neurons in the arcuate nucleus, e.g. by an excitatory amino acid, alters gastrointestinal function. In the present study, we investigated the effect of an excitatory amino acid, kainate, microinjected into the arcuate nucleus on gastric acid secretion in urethane-anesthetized rats. Kainate (140 pmol/rat) bilaterally microinjected into the Arc induced an significant inhibition of pentagastrin (PG) stimulated (16 mg/kg per h) gastric acid secretion throughout an observation period of 120 min after microinjection. Microinjection of kainate into hypothalamic areas outside the arcuate nucleus did not modify gastric secretion. Bilateral cervical vagotomy blocked the effect of kainate injected into the Arc on PG-stimulated gastric acid secretion. These data show that gastric secretory function can be modulated by stimulation of neuronal activity in the Arc via efferent vagal pathways. The results suggest that the arcuate nucleus is a forebrain area involved in the CNS regulation of gastrointestinal function.     

Effect of intrathecal proctolin administration on the behaviour evoked by the thyrotrophin-releasing hormone (TRH) analogue (RX 77368) and the indoleamine, TRH, substance P and calcitonin gene-related peptide levels and choline acetyltransferase activity in the rat spinal cord

The behavioral effects and the biochemical changes produced following either a single or repeated intrathecal injection respectively, of the insect peptide proctolin (Arg-Tyr-Leu-Pro-Thr-OH) have been compared with the effects of a stable analogue of thyrotrophin-releasing hormone (TRH) in rats. Intrathecal proctolin (1-100 micrograms) did not produce any marked behavioural effects on its own, while intrathecal TRH analogue (RX 77368, 0.5 microgram) administration produced wet-dog shakes and forepaw-licking behaviours. Proctolin (10 micrograms) significantly attenuated the wet-dog shake and forepaw-licking behaviours evoked by intrathecal RX 77368 administration when it was given 30 min before, but not when given in combination with RX 77368. Repeated intrathecal proctolin administration (10 micrograms twice daily for 5 days) significantly reduced the 5-hydroxytryptamine (5-HT), 5-hydroxyindoleacetic acid and TRH levels in the ventral, but not in the dorsal, horn of the spinal cord nor in the brainstem, and elevated hypothalamic TRH without affecting plasma free thyroxine levels when compared with values in saline-treated controls. Repeated proctolin injection did not alter substance P levels in any brain region examined, nor did it affect the choline acetyltransferase activity or the calcitonin gene-related peptide-like immunoreactive levels in the ventral horn of the spinal cord, both of which are principally located in motoneurones in this cord region.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of a thyrotropin releasing hormone analogue on locomotor and other motor activity in the rat

In the present experiments, locomotion has been studied in rats after injection of TRH analogue RX77368 (10 mg/kg i.p.). The measure used was the frequency of the cyclic shifts of weight from side to side (WTF) which accompany the progress of locomotion. It therefore provides an indirect measure of stepping frequency. After injection of RX77368 there was a shift in WTFs towards higher frequencies, i.e. when the rat walked it was taking more steps per second. These results suggest that RX77368 stimulates basic motor patterns associated with locomotion. The results obtained in these experiments are compared with those obtained using different quantification methods for locomotion and there is speculation concerning the possible modes of action of RX77368 including interactions with other neurotransmitter systems.     

PYY and NPY: control of gastric motility via action on Y1 and Y2 receptors in the DVC

The pancreatic polypeptide family of hormones and neurotransmitters including pancreatic polypeptide (PP), peptide YY (PYY) and neuropeptide Y (NPY) are emerging as potent central regulators of gastric function. There is, however, considerable debate concerning the mechanisms and even the direction of effects mediated by these peptides. Good evidence exists showing that PYY is the ‘enterogastrone’ released by the ileum after feeding which acts on vagal reflex control circuits to reduce gastric motility (i.e. the ‘ileal brake’). However, equally convincing evidence is available to suggest that PYY and its close structural relative NPY may act in the same region of the brain to increase gastric motility through vagal mechanisms. We hypothesize that the confounding observations are due to agonist effects on two different receptor types – Y1 and Y2, which are both present in the dorsal vagal complex (DVC) but may be accessed differentially by peripheral humoral (PYY) vs central (NPY) pathways. In our initial approach to this problem, we studied the effects of NPY, PYY, Y1 and Y2 agonists microinjected into the DVC on gastric motility in the stimulated (by central thyrotropin-releasing hormone (TRH)) and basal conditions. Our results show that Y2 agonist applied to the DVC during conditions of TRH-stimulated gastric motility mimicked the suppressive effects of PYY applied under the same conditions. Under basal conditions, Y2 agonist has no effect on motility. The DVC effect of the Y1 agonist is the opposite; Y1 agonist has no further effect to stimulate gastric motility in the TRH stimulated condition while Y1 agonist strongly stimulates motility from the basal condition. The effects of NPY depend upon the condition of study. Under TRH stimulation (maximal motility), NPY in the DVC reduces (but does not completely suppress) gastric motility while in the basal state, NPY is a strong activator of motility. These results are discussed in terms of the possible differential localization of Y1 vs Y2 receptors within the DVC and in terms of recent findings suggesting that PYY is rapidly converted to a Y2 agonist by a ubiquitous dipeptidyl aminopeptidase (DAP-IV).     

Intracisternal PYY inhibits gastric lesions induced by ethanol in rats: role of PYY-preferring receptors?

We previously reported that intracisternal (i.c.) injection of peptide YY (PYY) and low doses of thyrotropin-releasing hormone (TRH) or TRH analog, RX 77368, increased the resistance of the gastric mucosa to ethanol injury through vagal pathways in rats. The gastroprotective effect of i.c. injection of PYY/neuropeptide NPY (NPY) agonists with differential in vitro affinity to the Y receptor subtypes was examined in urethane-anesthetized rats. Intragastric administration of ethanol (45%, 5 ml/kg) results in mucosal lesions covering 23+/-2% of the gastric corpus in 1 h. PYY (500 ng, i.c.) significantly reduced ethanol-induced gastric lesions by 52%. [Pro34]PYY (PYY-preferring/Y1/Y5/Y4 subtypes) injected i.c. at 50, 100, 200 or 500 ng, reduced dose dependently gastric lesions to 15.4+/-2.2%, 11.4+/-3.1%, 8.6+/-2.9% and 5.4+/-2.2%, respectively. PYY3-36, (Y2/Y4 subtypes), [Leu31, Pro34]NPY (Y1/Y5), NPY (Y3/Y1/Y5/Y2) and pancreatic polypeptide (PP, Y4) injected i.c. at 500 ng did not influence significantly ethanol-induced gastric lesions. Combined i.c. injection of RX 77368 (1 ng) and Pro34PYY (25 ng), at sub-threshold doses given singly, reduced ethanol-induced gastric injury to 12.9+/-2.3% while RX 77368 (1 ng) plus PYY3-36 (500 ng) or [Leu31, Pro34]NPY (25 ng) had no effect. These findings indicate that i.c. PYY-induced gastric protection against 45% ethanol is mediated by a Y receptor subtype which bears similarity with the putative PYY-preferring receptor and distinct from the currently defined Y1/Y5; in addition, there is a synergistic interaction between activation of this PYY-preferring receptor and i.c. TRH to increase the resistance of the gastric mucosa to injury caused by 45% ethanol.     

The ability of RX 77368 — A stabilised analogue of TRH — To provoke the secretion of prolactin and TSH in vivo

RX 77368, a stabilised analogue of TRH, has been evaluated for its ability to provoke the release of TSH and prolactin $\text{in}$$\text{vivo}$ after intravenous administration to rats and human volunteers. The analogue caused a doserelated release of TSH in both species. In rats the compound caused release of prolactin but the dose-response relationship was bi-phasic, so that large doses caused only a diminished response. The prolactin response in human volunteers was equivocal and further experiments will be necessary to define the effect. Despite its greater biological stability the potency, efficacy and duration of effect with RX 77368 was similar to that of TRH in both species. The manner in which further endocrine investigations may aid the clinical development of RX 77368 is discussed.     

Potentiation of motoneurone excitability by combined administration of 5-HT agonist and TRH analogue

Motoneurone field potentials have been recorded from the lumbar region of the spinal cord, to antidromic stimulation of a ventral root, in rats anaesthetised with urethane. Injection of the thyrotropin releasing hormone (TRH) analogue RX77368 (1mg/kg) plus the 5-hydroxytryptamine (5-HT) receptor agonist 5-methoxy-N, N-dimethyl-tryptamine (5MeODMT 0.4mg/kg) resulted in a potentiation of the increase in amplitude and duration of response, compared to when the drugs were given singly. These results are discussed in the context of possible interactions between 5-HT and TRH systems.     

Central administration of thyrotropin releasing hormone (TRH) and related peptides inhibits feeding behavior in the Siberian hamster

Centrally acting thyrotropin releasing hormone (TRH), independent of endocrine action, has been shown to regulate several metabolic and behavioral parameters in rats, including food intake and locomotor activity. The present study investigated and compared the effects of central TRH on feeding behavior in Siberian hamsters exposed to long (LP) or short (SP) photoperiods, which induce natural physiological states of obesity and leanness respectively. The effects of two TRH analogues, RX77368 (a metabolically stable TRH analogue) and TRH-Gly (an endogenous precursor to TRH with putative preferential action at the central TRH receptor, TRH-R2), were also investigated. All peptides were infused via the third ventricle (i.c.v.). Food intake was measured, and the proportion of time spent interacting with food, active or resting was scored. TRH (5 microg) significantly reduced food intake without producing associated changes in activity in hamsters maintained in both LP (p < 0.001) and SP (p < 0.05). A lower dose of TRH (0.5 microg) only decreased feeding significantly (p < 0.01) in hamsters exposed to SP, indicating that there may be an underlying difference in sensitivity to TRH depending on metabolic state. RX77368 (1 microg) produced substantial hypophagia (p < 0.001) and decreased the proportion of time spent interacting with food, but, unlike TRH, may produce this via an increase in locomotor activity. TRH-Gly (5 microg) produced a small decrease in food intake (p < 0.05), lasting for 6 h. We conclude that TRH and TRH analogues possess anorexigenic capacities in this species, with a likely site of action in the hypothalamus. Increased sensitivity to the hypophagic effects of central TRH may contribute to the long-term catabolic state induced by short photoperiods.     

Acute and chronic effects of intrathecal galanin on behavioural and biochemical markers of spinal motor function in adult rats.

The spinal motor effects of galanin, which co-exists with 5-hydroxytryptamine (5-HT) and thyrotrophin-releasing hormone (TRH) in bulbospinal raphe neurones innervating spinal motoneurones, were examined by administering this neuropeptide through indwelling intrathecal cannulae to conscious adult Wistar rats. The acute effect of intrathecal galanin on spontaneous motor behaviour and the motor behaviours (back muscle contractions and wet-dog shakes) elicited by intrathecal injection of the non-selective 5-HT receptor agonist, 5-methoxy-N, N'-dimethyltryptamine (5-MeODMT) or the TRH analogue, RX 77368 analogue, RX 77368 (pGlu-His-3,3'-dimethyl-ProNH2), respectively, and the chronic effect of galanin on neurochemical markers for bulbospinal raphe neurones and spinal motoneurones were determined. Intrathecal galanin (0.1 to 10 micrograms) did not produce any notable motor behaviours when given alone, but pretreatment with the neuropeptide (0.1 micrograms) significantly attenuated both the number of wet-dog shakes and the amount of forepaw-licking induced by RX 77368, without affecting 5-MeODMT-induced back muscle contractions. Repeated intrathecal galanin administration (1 microgram, twice daily for 5 d) significantly elevated 5-HT (but not 5-hydroxyindoleacetic acid) and substance P-like immunoreactive (LI) levels and choline acetyltransferase (ChAT) activity in the dorsal, but not in the ventral, portion of the thoraco-lumbar spinal cord. In contrast, chronic intrathecal galanin did not alter the TRH- or calcitonin gene-related peptide (CGRP)-LI levels in either spinal cord region.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dorsal medullary serotonin and gastric motility: enhancement of effects by thyrotropin-releasing hormone

The effects of serotonin (5-HT) and thyrotropin-releasing hormone (TRH) on gastric motility patterns were investigated. Microinjection of serotonin (8 pmol in 4 nl) into the dorsal motor nucleus of the vagus produced a small increase in motility and tone, an effect which declined with repeated injections. As demonstrated previously, TRH (1 nmol in 1 microliter) applied to the surface of the dorsal medulla evoked a large increase in gastric motility and tone. After gastric motility returned to baseline following the TRH injection, we found that subsequent 5-HT injections, which previously evoked small changes in motility and tone, now evoked large increases in these indices. TRH augmentation of 5-HT-mediated effects on autonomic nuclei may be a significant feature in the alterations in gastric function that accompany the sleep-waking cycle and stress-related gastric pathology.     

Stimulation of the nucleus raphe obscurus produces marked serotonin release into the dorsal medulla of fed but not fasted rats — glutamatergic dependence

Serotonin interacts with TRH at the dorsal vagal complex (DVC) to augment gastric functional parameters. To ascertain physiologic relevance, patterns of stimulated release at the terminal field were characterized. Stimulation of the nucleus raphe obscurus (nRO) by kainic acid (423 pmol/10 nl) produced marked release of serotonin into dorsal medullary dialysates containing the DVC in freely fed, but not 24-h fasted rats. Probe infusion of kynurenic acid (1 mM), but not acute bilateral cervical vagotomy attenuated nRO-stimulated serotonin release in fed animals. The results suggest that the fed state facilitates serotonin release into the dorsal medulla by a mechanism mediated by activation of excitatory amino acid receptors in the dorsal medulla. Enhanced serotonergic neurotransmission at the DVC may comprise a heretofore unrecognized component of the integrated vago-vagal response to a meal.