Biomedical subjects

Y Taché

Publications and source records attributed to Y Taché.

At least 19 recordsLinked to original sources

PubMed1999

Kainic acid into the parapyramidal region protects against gastric injury by ethanol.

Neurons in the parapyramidal region of the ventral medulla project to the dorsal vagal complex and intermediolateral column. Kainic acid (0.5-5.0 ng) microinjected unilaterally into the parapyramidal region reduced 45% ethanol-induced gastric lesions by 50-60% in urethane anesthetized rats. Microinjections at sites nearby, but outside of the parapyramidal region, had no effect. These results provide the first evidence that the activation of parapyramidal region neurons influences gastric function and suggests a possible role of this ventral medulla region in gastric regulation.

Analysis of Variance↗

PubMed1999

Differential effects of chemical and mechanical colonic irritation on behavioral pain response to intraperitoneal acetic acid in mice.

Abdominal contractions are a viscerosomatic reflex response to noxious colorectal irritation in rats. In this study we characterize the modulating effect of chemical and mechanical colonic irritation on this reflex response to peritoneal irritation induced by diluted acetic acid (HAc) in conscious C57BL/6N mice. Pain responses were scored by counting the number of abdominal contractions during the 30-min period after intraperitoneal (i.p.) injection of either vehicle or HAc. Abdominal contractions were induced by 0.6% but not by 0.3% HAc. Chemical irritation of the colon by intraluminal 25% turpentine did not produce abdominal contractions by itself, but significantly increased the effect of both 0.3 and 0.6% i.p. HAc, administered 60 min after the luminal stimulus. Mechanical stimulation of the anorectum and colon by insertion of a balloon did not modify the effect of 0.6% HAc, while the insertion plus the inflation to 0.1 and 0.2 ml (30 s on/30 s off for 10 min) reduced the response to i.p. HAc by 35 and 88%, respectively. This inhibitory effect was reversed by naloxone (5 mg/kg, s.c.) pretreatment, while naloxone alone did not modify the effect of 0.6% HAc. These results demonstrate that chemical irritation of visceral afferents in the colonic mucosa and peritoneum of mice interact to enhance viscerosomatic pain responses, while the activation of colonic mechanoreceptors inhibits peritoneal irritation-induced pain responses and induces a freezing behavior by a naloxone-sensitive mechanism.

Abdominal Muscles↗

PubMed1999

Susceptibility of Lewis and Fischer rats to stress-induced worsening of TNB-colitis: protective role of brain CRF.

We assessed the role of central corticotropin-releasing factor (CRF) in stress-induced worsening of colitis in inbred rat strains with hypo (Lewis/N) and hyper (Fischer344/N) CRF responses to stress. Intracolonic administration of 2,4,6-trinitrobenzenesulfonic acid (TNB) induced colitis of similar severity in both strains as assessed on day 7 by macroscopic scoring, histological evaluation, tissue myeloperoxidase (MPO) activity, and decrease in food intake and body weight. Colitis was inhibited by daily intracerebroventricular injections of CRF in both strains. Chronic stress (3 h/day, water avoidance or wrap restraint on alternate days for 6 days) aggravated colitis more in Lewis than Fischer rats (71 and 22% further increase in MPO activity, respectively). The CRF antagonist astressin injected intracerebroventricularly enhanced the colitis response to stress and caused mortality in both strains. Fischer rats had higher plasma corticosterone levels 20 min after stress alone on day 1 and after TNB plus stress on days 1 and 3 compared with Lewis. These data show that central CRF restrains the proinflammatory action of stress in experimental colitis.

Animals↗

PubMed1999

Peripheral urocortin delays gastric emptying: role of CRF receptor 2.

Urocortin, a new mammalian member of the corticotropin-releasing factor (CRF) family has been proposed to be the endogenous ligand for CRF receptor 2 (CRF-R2). We studied the influence of intravenous urocortin on gastric emptying and the role of CRF-R2 in peptide action and postoperative gastric ileus in conscious rats. The intravenous doses of rat CRF and rat urocortin producing 50% inhibition of gastric emptying were 2.5 and 1.1 microgram/kg, respectively. At these intravenous doses, CRF and urocortin have their actions fully reversed by the CRF-R1/CRF-R2 antagonist astressin at antagonist/agonist ratios of 5:1 and 67:1, respectively. Astressin (12 microgram/kg iv) completely prevented abdominal surgery-induced 54% inhibition of gastric emptying 3 h after surgery while having no effect on basal gastric emptying. The selective nonpeptide CRF-R1 antagonists antalarmin (20 mg/kg ip) and NBI-27914 (400 microgram/kg iv) did not influence intravenous CRF-, urocortin- or surgery-induced gastric stasis. These results as well as earlier ones showing that alpha-helical CRF9-41 (a CRF-R2 more selective antagonist) partly prevented postoperative ileus indicate that peripheral CRF-R2 may be primarily involved in intravenous urocortin-, CRF-, and abdominal surgery-induced gastric stasis.

Animals↗

PubMed1999

Intracisternal TRH analog increases gastrin release and corpus histidine decarboxylase activity in rats.

Thyrotropin-releasing hormone (TRH) acts in brain stem nuclei to induce vagally mediated stimulation of gastric secretion. The effects of intracisternal injection of the TRH analog RX-77368 on plasma gastrin levels and corpus histidine decarboxylase (HDC) activity were studied in 48-h fasted conscious rats. RX-77368 (25-100 ng) increased plasma gastrin levels by threefold at 30 min, which remained significantly higher than control at 2 and 4 h postinjection. Corpus HDC activity began to increase at 2 h and reached a peak at 4 h postinjection with a 21-fold maximum response observed at 50 ng. Morphological changes in the appearance of corpus HDC-immunoreactive cells correlated well with HDC activity. Pretreatment with gastrin monoclonal antibody completely prevented RX-77368 stimulatory effects on HDC activity. Atropine significantly attenuated gastrin increase at 30 min by 26%. These results indicated that in conscious fasted rats, TRH analog acts in the brain to increase corpus HDC activity in the enterochromaffin-like cells, which involves gastrin release stimulated by central TRH analog.

Animals↗

PubMed1999

Central autonomic activation by intracisternal TRH analogue excites gastric splanchnic afferent neurons.

Intracisternal (ic) injection of thyrotropin-releasing hormone (TRH) or its stable analogue RX 77368 influences gastric function via stimulation of vagal muscarinic pathways. In rats, the increase in gastric mucosal blood flow evoked by a low ic dose of RX 77368 occurs via release of calcitonin gene-related peptide from capsaicin-sensitive afferent neurons, most probably of spinal origin. In this study, the effect of low ic doses of RX 77368 on afferent impulse activity in splanchnic single fibers was investigated. The cisterna magna of overnight-fasted, urethan-anesthetized Sprague-Dawley rats was acutely cannulated, and fine splanchnic nerve twigs containing at least one fiber responsive to mechanical probing of the stomach were isolated at a site immediately distal to the left suprarenal ganglion. Unit mechanoreceptive fields were encountered in all portions of the stomach, both superficially and in deeper layers. Splanchnic afferent unit impulse activity was recorded continuously during basal conditions and in response to consecutive ic injections of saline and RX 77368 (15-30 min later; 1.5 or 3 ng). Basal discharge rates ranged from 0 to 154 impulses/min (median = 10.2 impulses/min). A majority of splanchnic single units with ongoing activity increased their mean discharge rate by >/=20% after ic injection of RX 77368 at either 1.5 ng (6/10 units; median increase 63%) or 3 ng (19/24 units; median increase 175%). Five units lacking impulse activity in the 5-min before ic RX 77368 (3 ng) were also excited, with the onset of discharge occurring within 1.0-5.0 min postinjection. In units excited by ic RX 77368, peak discharge occurred 15.6 +/- 1.3 min after injection and was followed by a decline to stable activity levels </=20-40 min thereafter. In a few cases (4/24), ic RX 77368 (3 ng) inhibited the impulse activity of initially active units, with a time course comparable to that seen in units excited by the same treatment. The pattern of discharge in most units was not suggestive of mechanical modulation of activity by rhythmic gastric contractions. The data demonstrate that low ic doses of TRH analogue induce sustained increases in afferent discharge in a substantial proportion of splanchnic neurons innervating the rat stomach. These findings support the notion that splanchnic afferent excitation occurs concomitantly with vasodilatory peptide release from gastric splanchnic afferent nerve terminals after ic TRH-induced autonomic activation.

Animals↗

PubMed1999

Corticotropin-releasing factor and the brain-gut motor response to stress.

The characterization of corticotropin-releasing factor (CRF) and CRF receptors, and the development of specific CRF receptor antagonists selective for the receptor subtypes have paved the way to the understanding of the biochemical coding of stress-related alterations of gut motor function. Reports have consistently established that central administration of CRF acts in the brain to inhibit gastric emptying while stimulating colonic motor function through modulation of the vagal and sacral parasympathetic outflow in rodents. Endogenous CRF in the brain plays a role in mediating various forms of stressor-induced gastric stasis, including postoperative gastric ileus, and activates colonic transit and fecal excretion elicited by psychologically aversive or fearful stimuli. It is known that brain CRF is involved in the cross-talk between the immune and gastrointestinal systems because systemic or central administration of interleukin-1-beta delays gastric emptying while stimulating colonic motor activity through activation of CRF release in the brain. The paraventricular nucleus of the hypothalamus and the dorsal vagal complex are important sites of action for CRF to inhibit gastric motor function, while the paraventricular nucleus of the hypothalamus and the locus coeruleus complex are sites of action for CRF to stimulate colonic motor function. The inhibition of gastric emptying by CRF may be mediated by the interaction with the CRF2 receptors, while the anxiogenic and colonic motor responses may involve CRF1 receptors. Hypersecretion of CRF in the brain may contribute to the pathophysiology of stress-related exacerbation of irritable bowel syndrome.

Animals↗

PubMed1999

Feedback regulation of thyrotropin-releasing hormone gene expression by thyroid hormone in the caudal raphe nuclei in rats.

Medullary TRH regulates autonomic activity, and altered thyroid status is associated with autonomic disorders. We investigated whether thyroid hormone exerts a negative feedback regulation on TRH gene expression in the medullary caudal raphe nuclei. Medullary pro-TRH messenger RNAs (mRNAs) were mainly located in the raphe pallidus and raphe obscurus neurons as shown by in situ hybridization and were significantly increased by 70% and 160-230% by Northern blot analyses in 24 h fasted rats at 1 and 3-5 weeks after thyroidectomy, respectively, when serum T4 levels were reduced by 75-87%. The increased pro-TRH mRNA on the 30th day after thyroidectomy was reversed to euthyroid levels by T4 replacement (2 or 4 microg/100 g x day). T4 injections (10 or 100 microg/100 g x day for 30 days) did not significantly influence medullary pro-TRH mRNA levels in sham-operated rats. Thyroidectomized rats fed normally showed a 500% increase in pro-TRH mRNA levels 30 days after the surgery, while those fasted for 24 h showed only a 180% increase. These data indicate that medullary TRH gene expression is enhanced during hypothyroidism due to the lack of negative feedback regulation by thyroid hormone, and this response is modulated by feeding state. These findings may have important relevance to understanding autonomic-related visceral alterations induced by hypothyroidism.

Animals↗

PubMed1999

Peripheral injection of a new corticotropin-releasing factor (CRF) antagonist, astressin, blocks peripheral CRF- and abdominal surgery-induced delayed gastric emptying in rats.

The effect of the corticotropin-releasing factor (CRF) receptor antagonists astressin and D-Phe CRF(12-41) injected i.v. on CRF-induced delayed gastric emptying (GE) was investigated in conscious rats. Gastric transit was assessed by the recovery of methyl cellulose/phenol red solution 20 min after its intragastric administration. The 55% inhibition of GE induced by CRF (0.6 microgram i.v.) was antagonized by 87 and 100% by i.v. astressin at 3 and 10 microgram, respectively, and by 68 and 64% by i.v. D-Phe CRF(12-41) at 10 and 20 microgram, respectively. CRF (0.6 microgram)-injected intracisternally (i.c.) induced 68% reduction of GE was not modified by i.v. astressin (10 microgram) whereas i.c. astressin (3 or 10 microgram) blocked by 58 and 100%, respectively, i.v. CRF inhibitory action. Abdominal surgery with cecal manipulation reduced GE to 7.1 +/- 3.1 and 27.5 +/- 3.3% at 30 and 180 min postsurgery, respectively, compared with 40.3 +/- 4.3 and 59.5 +/- 2.9% at similar times after anesthesia alone. Astressin (3 microgram i.v.) completely and D-Phe CRF(12-41) (20 microgram i.v.) partially (60%) blocked surgery-induced gastric stasis observed at 30 or 180 min. The CRF antagonists alone (i.v. or i.c.) had no effect on basal GE. These data indicate that CRF acts in the brain and periphery to inhibit GE through receptor-mediated interaction and that peripheral CRF is involved in acute postoperative gastric ileus; astressin is a potent peripheral antagonist of CRF when injected i.v. whereas i.c. doses >/=3 microgram exert dual central and peripheral blockade of CRF action on gastric transit.

Animals↗

PubMed1998

Astressin analogues (corticotropin-releasing factor antagonists) with extended duration of action in the rat.

In earlier reports we identified specific point substitutions (DPhe12,Nle21,38), cyclization strategies [in particular, introduction of lactam rings such as that of cyclo(Glu30,Lys33)], and deletions (residues 1-7) in the CRF molecule that led to agonists. We also noted that further deletions (residues 8-14) produced antagonists such as astressin ¿cyclo(30-33)[DPhe12,Nle21,38, Glu30, Lys33]hCRF(12-41)¿ (1). We hypothesized that the lactam ring promoted conformational stability to yield analogues with increased potency both in vitro and in vivo as compared to that of their linear counterparts. Additionally, we reported that cyclo(30-33)[DPhe12,Nle21,38, Glu30,DHis32,Lys33]hCRF(12-41) (3) and dicyclo(26-36,30-33)[Ac-Asp9,DPhe12,Nle21,38, Cys26, Glu30,Lys33, Cys36]hCRF(9-41) were ca. twice and 1/100 as potent as astressin, respectively, suggesting a putative turn that encompasses residues 30-33 (previous paper: Koerber et al. J. Med. Chem. 1998, 41). To increase the potency of 1 and/or 3 in vivo, we extended their chain length by one (5-8), two (9, 10), and three (11, 12) residues at the N-terminus and acetylated (6, 8, 10, 12). Of the compounds tested for duration of action (1, 3-6, 8), we found 6 and 8 to be slightly longer-acting than astressin or [DHis32]astressin, while their potencies in vitro were not significantly different from that of 3. Additionally, we introduced CalphaMe-leucine residues in lieu of leucine at positions 14, 15, 19, 27, and 37 in [DHis32]astressin. The analogue [CalphaMe-Leu27,DHis32]astressin (16) was more potent (although not statistically in all cases) than the other four analogues in vitro. While acetylation of the N-terminus of 16 (i.e., 18) or of [CalphaMe-Leu27]astressin (i.e., 19) did not have a significant effect on in vitro potency, elongation of the N-terminus by one or three residues in addition to acetylation resulted in cyclo(30-33)[DPhe12,Nle21,CalphaMe-Leu27,Glu3 0,DHis32,Lys33, Nle38]Ac-hCRF(11-41) (21), cyclo(30-33)[DPhe12,Nle21,CalphaMe-Leu27, Glu30,Lys33,Nle38]Ac-hCRF(9-41) (22), and cyclo(30-33)[DPhe12, Nle21, CalphaMe-Leu27,Glu30,DHis32,Lys33,Nle38 ]Ac-hCRF(9-41) (23) that were longer-acting than 6 and 8 (ca. 2 h inhibition of ACTH secretion at 25 micrograms/adrenalectomized rat). Analogues 22 and 23 were also more potent than astressin at reversing intracisternal CRF- and abdominal surgery-induced delay of gastric emptying in conscious rats.

Adrenalectomy↗

PubMed1998

Fos expression in the brain induced by peripheral injection of CCK or leptin plus CCK in fasted lean mice.

We previously reported a synergistic interaction between leptin and cholecystokinin (CCK) to reduce food intake through CCK-A receptors in lean mice fasted for 24 h. To identify the activated neuronal pathways, we investigated changes in Fos expression in brain nuclei 2 h after single or combined intraperitoneal (i.p.) injections of leptin (120 microg/kg) and sulfated CCK-8 (3.5 microg/kg) in male lean mice (C57BL/6) fasted for 24 h using immunohistochemistry for Fos, the protein product of the early gene, c-fos. Leptin did not increase Fos expression in the brain compared with vehicle-treated mice. CCK increased the numbers of Fos-positive neurons in the nucleus of the solitary tract (NTS)/area postrema (AP), central nucleus of the amygdala (CeA) and, to a smaller extent, in the paraventricular nucleus of the hypothalamus (PVN) (5.2-, 2.3- and 0. 3-fold respectively). Injections of leptin-CCK further enhanced Fos expression by 40% in the PVN compared with that induced by CCK alone, but not in the other nuclei. Devazepide (a CCK-A receptor antagonist, 1 mg/kg, i.p.) prevented the increase in Fos expression induced by leptin-CCK in the PVN and by CCK alone in the PVN, CeA and NTS/AP. These results indicate that in fasted mice, i.p. injection of CCK increases Fos expression in specific brain nuclei through CCK-A receptors while leptin alone had no effect. Leptin in conjunction with CCK selectively enhanced Fos expression in the PVN. The PVN may be an important site mediating the synergistic effect of leptin-CCK to regulate food intake.

Adipose Tissue↗

PubMed1998

Proximal colon distention increases Fos expression in the lumbosacral spinal cord and activates sacral parasympathetic NADPHd-positive neurons in rats.

Fos expression induced by nociceptive mechanical distention of the proximal colon was examined in the lumbosacral spinal cord in freely moving rats equipped with a chronic balloon in the proximal colon. Fos protein in lumbosacral neurons was detected immunocytochemically, and colocalization with nicotinamide adenine dinucleotide phosphate diaphorase (NADPHd) activity was determined histochemically at 1 hour after distention. Distention of the proximal colon (10 ml, 30 seconds on/off for 10 minutes, about 90 mm Hg) increased the number of Fos-positive cells in the lumbar 6 (L6) and sacral 1 and 2 (S1, S2) segments, whereas no change was observed in the L1-L5 and S3 segments compared with the sham distended group or with animals that received no treatment. In L6-S2 segments, Fos-positive neurons were increased by two-fold in laminae I-VII (mainly in laminae I and outer II) and area X (surrounding the central canal) and by nine-fold in the sacral parasympathetic nucleus. Results of time course studies indicate that the maximal increase in Fos expression observed at 1 hour after distention returns to basal levels within 4 hours. In the S1 segment, distention of the proximal colon increased the percentage of NADPHd/Fos-positive neurons selectively in the parasympathetic nucleus by 40% compared with less than 4% in the sham distention group; the number and pattern of NADPHd-stained cells were not modified. These results indicate that noxious distention of the proximal colon for a short duration in awake rats selectively activates neurons in the L6-S2 segments of the dorsal horn mainly in laminae involved in nociceptive and autonomic processing. The marked activation of NADPHd-positive neurons in the sacral parasympathetic nucleus suggests a possible role of nitric oxide in the visceroautonomic reflexes induced by distention of the proximal colon.

Animals↗

PubMed1998

High basal gastric acid secretion in somatostatin receptor subtype 2 knockout mice.

BACKGROUND & AIMS: Somatostatin receptor subtype 2 (sst2) agonists inhibit gastric secretion. The role of sst2 in the regulation of acid secretion was assessed using sst2 knockout mice and urethane to induce somatostatin release. METHODS: Acid secretion was monitored every 10 minutes by gastric perfusion and backtitration of perfusates in fasted, urethane-anesthetized C57/129 sst2 (-/-) mice and wild-type (+/+) mice. The ileal vein was cannulated for drug injection. Intragastric pH and serum gastrin were monitored 1 hour after anesthesia without perfusion. RESULTS: Gastric pH values were lower in sst2 (-/-) mice (3.8 +/- 0.3) than in wild-type mice (7.1 +/- 0.1, P < 0.05), and there was no difference in gastrin levels. Basal acid output per 2 hours was 10-fold higher in sst2 knockout mice compared with wild-type mice. The gastrin antibody abolished the high basal acid secretion in sst2 (-/-) mice and had no effect in wild-type mice. The somatostatin antibody increased basal secretion by 4-fold in wild-type and had no effect in knockout mice. Somatostatin 14 or the sst2 agonist DC 32-87 inhibited pentagastrin-stimulated acid secretion in wild-type mice, but did not alter basal secretion in knockout mice. CONCLUSIONS: These results indicate that sst2 is the main subtype whereby endogenous somatostatin suppresses gastric acid secretion through inhibition of gastrin action.

Animals↗

PubMed1998

PYY-preferring receptor in the dorsal vagal complex and its involvement in PYY stimulation of gastric acid secretion in rats.

1. Microinjection of peptide YY (PYY, 7-46 pmol) into the dorsal vagal complex (DVC) stimulated gastric acid secretion in urethane-anaesthetized rats. Using a variety of neuropeptide Y (NPY) and PYY derivatives, we characterized the pharmacological profile of the receptor mediating the acid secretory response to PYY. 2. [Pro34]rat(r)/porcine(p)PYY and [Pro34]human(h)PYY (23-117 pmol), microinjected unilaterally into the DVC resulted in a similar maximal increase in net acid secretion reaching 68+/-11 and 89+/-31 micromol 90 min(-1) respectively. 3. Rat/hNPY and pNPY (47 pmol) microinjected into the DVC induced a similar net gastric acid secretion (27+/-8 and 23+/-8 micromol 90 min(-1) respectively) and a higher dose (116 pmol) tended to reduce the response. 4. Pancreatic polypeptide (PP, 4-46 pmol), [Leu31,Pro34]r/hNPY (47 and 117 pmol) and the Y2 selective agonists, hPYY3-36, pNPY5-36 and PNPY13-36 (25-168 pmol) microinjected into the DVC failed to influence basal gastric acid secretion. 5. The rank order of potency of PYY > or = [Pro34]r/pPYY = [Pro34]hPYY> r/hNPY = pNPY to stimulate gastric acid secretion upon injection into the DVC and the ineffectiveness of PP, [Leu31,Pro34]NPY and C-terminal NPY/PYY fragments suggest that a PYY-preferring receptor subtype may be involved in mediating the stimulating effect.

Animals↗

PubMed1998

Peripheral mediators involved in gastric hyperemia to vagal activation by central TRH analog in rats.

Mechanisms mediating the increase in gastric mucosal blood flow (GMBF) induced by the stable thyrotropin-releasing hormone (TRH) analog RX-77368 injected intracisternally at a gastric acid secretory dose (30 ng) were investigated using hydrogen gas clearance in urethan-anesthetized rats. The histamine H1 receptor antagonist pyrilamine (intravenously), capsaicin (subcutaneously, 10 days), and NG-nitro-L-arginine methyl ester (L-NAME, intracisternally) failed to impair the 150% rise in GMBF induced by intracisternal injection of RX-77368. By contrast, atropine (subcutaneously) and NG-monomethyl-L-arginine (intravenously) completely inhibited the increase in GMBF evoked by intracisternal RX-77368. L-NAME (intravenously) blocked the intracisternal RX-77368-induced increase in GMBF in capsaicin-pretreated rats, and the L-NAME effect was reversed by intravenous L- but not D-arginine. These findings indicate that vagal efferent activation induced by TRH analog injected intracisternally at a gastric acid secretory dose increases GMBF through atropine-sensitive mechanisms stimulating L-arginine-nitric oxide pathways, whereas H1 receptors and capsaicin-sensitive afferent fibers do not play a role.

Animals↗

PubMed1998

Central CRF inhibits gastric emptying of a nutrient solid meal in rats: the role of CRF2 receptors.

Corticotropin-releasing factor (CRF)-related peptides exhibit different affinity for the receptor subtypes 1 and 2 cloned in the rat brain. We investigated, in conscious rats, the effects of intracisternal (i.c.) injection of CRF (rat/human) on the 5-h rate of gastric emptying of a solid nutrient meal (Purina chow and water ad libitum for 3 h) and the CRF receptor subtype involved. CRF, urotensin I (suckerfish), and sauvagine (frog) injected i.c. inhibited gastric emptying in a dose-dependent manner, with ED50 values of 0.31, 0.13, and 0.08 microgram/rat, respectively. Rat CRF-(6-33) (0.1-10 micrograms i.c.) had no effect. The nonselective CRF1 and CRF2 receptor antagonist, astressin, injected i.c. completely blocked the inhibitory effect of i.c. CRF, urotensin I, and sauvagine with antagonist-to-agonist ratios of 3:1, 10:1, and 16:1, respectively. The CRF1-selective receptor antagonist NBI-27914 injected i.c. at a ratio of 170:1 had no effect. These data show that central CRF and CRF-related peptides are potent inhibitors of gastric emptying of a solid meal with a rank order of potency characteristic of the CRF2 receptor subtype affinity (sauvagine > urotensin I > CRF). In addition, the reversal by astressin but not by the CRF1-selective receptor antagonist further supports the view that the CRF2 receptor subtype is primarily involved in central CRF-induced delayed gastric emptying.

Amphibian Proteins↗

PubMed1998

Vagal mechanisms underlying gastric protection induced by chemical activation of raphe pallidus in rats.

Peripheral mechanisms involved in kainic acid injected into the raphe pallidus (Rpa)-induced gastric protection were investigated in urethan-anesthetized rats. Gastric mucosal blood flow (GMBF), acid secretion, and gastric injury induced by intragastric ethanol (60%) were measured in response to kainic acid (25 pg) injected into the Rpa. Kainic acid reduced ethanol-induced gastric lesions by 57%. The protective effect was blocked by vagotomy, capsaicin deafferentation, and intravenous injection of the calcitonin gene-related peptide (CGRP) antagonist CGRP-(8-37) and NG-nitro-L-arginine methyl ester (L-NAME). L- but not D-arginine reversed the L-NAME action. Kainic acid injected into the Rpa, unlike outside sites, increased basal GMBF but not acid secretion. Indomethacin unmasked an acid secretory response to kainic acid. These results show that kainic acid injected into the Rpa at a dose that did not stimulate acid secretion, due to the inhibitory effect of prostaglandins, protects against ethanol-induced gastric injury through vagal-dependent activation of CGRP contained in capsaicin-sensitive afferents and nitric oxide-mediated gastric vasodilatory mechanisms.

Afferent Pathways↗

PubMed1998

Intracisternal antisense oligodeoxynucleotides to the thyrotropin-releasing hormone receptor blocked vagal-dependent stimulation of gastric emptying induced by acute cold in rats.

Cold exposure increases TRH gene expression in hypothalamic and raphe nuclei and results in a vagal activation of gastric function. We investigated the role of medullary TRH receptors in cold (4-6 C, 90 min)-induced stimulation of gastric motor function in fasted conscious rats using intracisternal injections of TRH receptor (TRHr) antisense oligodeoxynucleotides (100 microg twice, -48 and -24 h). The gastric emptying of a methyl-cellulose solution was assessed by the phenol red method. TRH (0.1 microg) or the somatostatin subtype 5-preferring analog, BIM-23052 (1 microg), injected intracisternally increased basal gastric emptying by 34% and 47%, respectively. TRHr antisense, which had no effect on basal emptying, blocked TRH action but did not influence that of BIM-23052. Cold exposure increased gastric emptying by 64%, and the response was inhibited by vagotomy, atropine (0.1 mg/kg, i.p.), and TRHr antisense (intracisternally). Saline or mismatched oligodeoxynucleotides, injected intracisternally under similar conditions, did not alter the enhanced gastric emptying induced by cold or intracisternal injection of TRH or BIM-23052. These results indicate that TRH receptor activation in the brain stem mediates acute cold-induced vagal cholinergic stimulation of gastric transit, and that medullary TRH may play a role in the autonomic visceral responses to acute cold.

Animals↗