Low doses of TRH analogue act in the dorsal motor nucleus to induce gastric protection in rats

Mechanisms involved in central thyrotropin-releasing hormone (TRH) analogue RX-77368-induced prevention of gastric lesions were investigated in urethan-anesthetized rats. Gastric lesions were induced by intragastric administration of ethanol (4 ml/kg) and assessed 1 h later by macroscopic visualization using computerized image analysis. RX-77368 (3, 5, and 10 ng) microinjected into the dorsal motor nucleus of the vagus (DMN) decreased ethanol-induced gastric lesions by 79, 68, and 61%, respectively. RX-77368 at 1.5, 15, or 30 ng into the DMN or at 3 or 10 ng into the nucleus of the solitary tract, hypoglossal nucleus, or reticular field was ineffective in preventing mucosal damage. The protective effect of RX-77368 (3 ng into the DMN) was partly inhibited by peripheral injection of indomethacin and completely blocked by atropine, the calcitonin gene-related peptide antagonist, CGRP-(8-37), and NG-nitro-L-arginine methyl ester (L-NAME). L-arginine, but not D-arginine, reversed the effect of L-NAME. RX-77368 (3 ng into the DMN) enhanced gastric prostaglandin E2 (PGE2) release. These data indicate that low doses of TRH analogue act in the DMN to induce gastric protection against ethanol injury through muscarinic-, PGE2-, CGRP-, and nitric oxide-dependent mechanisms.

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Postnatal developmental expressions of neurotransmitters and receptors in various brain stem nuclei of rats

Journal of Applied Physiology ◽

10.1152/japplphysiol.01301.2004 ◽

2005 ◽

Vol 98 (4) ◽

pp. 1442-1457 ◽

Cited By ~ 74

Author(s):

Qiuli Liu ◽

Margaret T. T. Wong-Riley

Keyword(s):

Brain Stem ◽

Respiratory Control ◽

Nucleus Ambiguus ◽

Hypoglossal Nucleus ◽

Motor Nucleus ◽

Developmental Trend ◽

Receptor Subunit ◽

Cuneate Nucleus ◽

Glycine Receptors ◽

Dorsal Motor Nucleus

Previously, we reported that the expression of cytochrome oxidase in a number of brain stem nuclei exhibited a plateau or reduction at postnatal day (P) 3–4 and a dramatic decrease at P12, against a general increase with age. The present study examined the expression of glutamate, N-methyl-d-aspartate receptor subunit 1 (NMDAR1), GABA, GABAB receptors, glycine receptors, and glutamate receptor subunit 2 (GluR2) in the ventrolateral subnucleus of the solitary tract nucleus, nucleus ambiguus, hypoglossal nucleus, medial accessory olivary nucleus, dorsal motor nucleus of the vagus, and cuneate nucleus, from P2 to P21 in rats. Results showed that 1) the expression of glutamate increased with age in a majority of the nuclei, whereas that of NMDAR1 showed heterogeneity among the nuclei; 2) GABA and GABAB expressions decreased with age, whereas that of glycine receptors increased with age; 3) GluR2 showed two peaks, at P3–4 and P12; and 4) glutamate and NMDAR1 showed a significant reduction, whereas GABA, GABAB receptors, glycine receptors, and GluR2 exhibited a concomitant increase at P12. These features were present but less pronounced in hypoglossal nucleus and dorsal motor nucleus of the vagus and were absent in the cuneate nucleus. These data suggest that brain stem nuclei, directly or indirectly related to respiratory control, share a common developmental trend with the pre-Bötzinger complex in having a transient period of imbalance between inhibitory and excitatory drives at P12. During this critical period, the respiratory system may be more vulnerable to excessive exogenous stressors.

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Cardiovascular responses to microinjection of ANF into dorsal medulla of rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1988.255.1.r182 ◽

1988 ◽

Vol 255 (1) ◽

pp. R182-R187 ◽

Cited By ~ 5

Author(s):

D. J. McKitrick ◽

F. R. Calaresu

Keyword(s):

Area Postrema ◽

Cardiovascular Responses ◽

Significant Decline ◽

Medial Longitudinal Fasciculus ◽

Hypoglossal Nucleus ◽

Cardiovascular Reflexes ◽

Motor Nucleus ◽

Cuneate Nucleus ◽

Dorsal Motor Nucleus ◽

Dorsal Medulla

Atrial natriuretic factor (ANF) has been suggested as a putative neurotransmitter in central pathways involved in the control of the cardiovascular system. To investigate this possibility, 50 nl of 10(-7) M ANF were microinjected into discrete sites in the nucleus of the tractus solitarius (NTS) where baro- and chemoreceptor afferents terminate. Injections into 36 of a total of 66 sites in the NTS of paralyzed artificially ventilated Wistar rats under urethan anesthesia were found to produce a significant decline in heart rate [HR; -9.2 +/- 2.9 (SE) beats/min, P less than 0.05] and mean arterial pressure [MAP; -11.1 +/- 1.2 (SE) mmHg, P less than 0.01]. Similar responses were also present in anesthetized animals breathing spontaneously. Microinjection of an inactive peptide analogue or of saline did not produce cardiovascular changes. It was also found that ANF injection into the cuneate nucleus (20 of 38 sites) and the spinal trigeminal complex (28 of 42 sites) produced a decrease in MAP and HR that were of the same magnitude as those seen in the NTS. Injections of ANF into the medial longitudinal fasciculus (n = 22), hypoglossal nucleus (n = 9), area postrema (n = 16), and dorsal motor nucleus of the vagus (n = 11) did not change HR or MAP. These results suggest that ANF may serve as a neurotransmitter involved in cardiovascular reflexes mediated by specific nuclei in the dorsal medulla.

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Medullary TRH is involved in gastric protection induced by low dose of kainic acid into the raphe pallidus

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1995.268.4.g548 ◽

1995 ◽

Vol 268 (4) ◽

pp. G548-G552 ◽

Cited By ~ 1

Author(s):

H. Kaneko ◽

H. Yang ◽

G. Ohning ◽

Y. Tache

Keyword(s):

Acid Secretion ◽

Kainic Acid ◽

Low Dose ◽

Protective Action ◽

Thyrotropin Releasing Hormone ◽

Motor Nucleus ◽

Gastric Lesions ◽

Cytoprotective Effect ◽

Dorsal Motor Nucleus ◽

Raphe Pallidus

The gastroprotective effect of kainic acid microinjected into the raphe pallidus (Rpa) at a dose subthreshold to increase acid secretion was investigated in urethan-anesthetized rats. Kainic acid (25 pg/30 nl) microinjected into the Rpa inhibited by 65.8% gastric damage induced by intragastric ethanol (60%). No protection was observed when kainic acid was injected outside of the Rpa. The cytoprotective effect was completely abolished by thyrotropin-releasing hormone (TRH) antibody microinjected bilaterally (1.3 micrograms/site) into the dorsal motor nucleus of the vagus (DMN), indomethacin (5 mg/kg ip), and atropine (0.3 mg/kg sc). Microinjection of TRH antibody outside of the DMN or of control antibody into the DMN did not modify the protective action induced by kainic acid into the Rpa. The TRH antibody microinjected alone into the DMN did not alter the severity of the ethanol-induced gastric lesions. These data indicate that excitation of Rpa neurons by a low dose of kainic acid results in cytoprotection against ethanol lesions. Furthermore, this cytoprotection occurs as a result of TRH action in the DMN and activation of muscarinic and prostaglandin pathways.

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Neurochemical studies of the nucleus of the solitary tract, dorsal motor nucleus of the vagus and the hypoglossal nucleus in rat: Topographical distribution of glutamate uptake, GABA uptake and glutamic acid decarboxylase activity

Brain Research Bulletin ◽

10.1016/0361-9230(85)90176-5 ◽

1985 ◽

Vol 14 (1) ◽

pp. 49-53 ◽

Cited By ~ 37

Author(s):

J.R. Simon ◽

S.K. DiMicco ◽

M.H. Aprison

Keyword(s):

Glutamic Acid Decarboxylase ◽

Glutamate Uptake ◽

Hypoglossal Nucleus ◽

Acid Decarboxylase ◽

Gaba Uptake ◽

Motor Nucleus ◽

Decarboxylase Activity ◽

Solitary Tract ◽

Dorsal Motor Nucleus ◽

Topographical Distribution

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Gastric Lesions Induced by Kainic Acid Injection into the Dorsal Motor Nucleus of the Vagus Nerve in Rats

Scandinavian Journal of Gastroenterology ◽

10.3109/00365528909091114 ◽

1989 ◽

Vol 24 (sup162) ◽

pp. 15-18 ◽

Cited By ~ 9

Author(s):

T. Okumura ◽

K. Okamura ◽

S. Kitamori ◽

H. Hara ◽

Y. Shibata ◽

...

Keyword(s):

Vagus Nerve ◽

Kainic Acid ◽

Motor Nucleus ◽

Gastric Lesions ◽

Acid Injection ◽

Dorsal Motor Nucleus ◽

Kainic Acid Injection

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Intracisternal PYY increases gastric mucosal resistance: role of cholinergic, CGRP, and NO pathways

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1999.277.3.g555 ◽

1999 ◽

Vol 277 (3) ◽

pp. G555-G562 ◽

Cited By ~ 3

Author(s):

Hong Yang ◽

Keishi Kawakubo ◽

Yvette Taché

Keyword(s):

Peptide Yy ◽

Antisense Oligodeoxynucleotide ◽

Intragastric Administration ◽

Gastric Lesions ◽

Protective Mechanisms ◽

Gastroprotective Effect ◽

Calcitonin Gene ◽

Cgrp Receptor Antagonist ◽

Synthase Inhibitor

The influence of intracisternal injection of peptide YY (PYY) on gastric lesions induced by ethanol was studied in urethan-anesthetized rats. Gastric lesions covered 15–22% of the corpus as monitored 1 h after intragastric administration of 45% ethanol (5 ml/kg) in intracisternal vehicle control groups. PYY, at doses of 23, 47, or 117 pmol 30 min before ethanol, decreased gastric lesions by 27%, 63%, and 59%, respectively. Thyrotropin-releasing hormone (TRH) receptor antisense oligodeoxynucleotide pretreatment (intracisternally, 48 and 24 h before intracisternal PYY) did not influence the gastroprotective effect of intracisternal PYY (47 pmol) but abolished that of intracisternal TRH analog RX-77368 (4 pmol). RX-77368 (2.6 pmol) and PYY (6 pmol) were ineffective when injected intracisternally alone but reduced ethanol lesions by 44% when injected simultaneously. Atropine (subcutaneously), the calcitonin gene-related peptide (CGRP) receptor antagonist CGRP-(8—37) (intravenously), or the nitric oxide (NO) synthase inhibitor N G-nitro-l-arginine methyl ester (l-NAME, intravenously) completely abolished the gastroprotective effect of intracisternal PYY (47 pmol), whereas indomethacin (intraperitoneally) had no effect. The l-NAME action was reversed by l-arginine but not by d-arginine (intravenously). These results suggest that intracisternal PYY acts independently of medullary TRH to decrease ethanol-induced gastric lesions. The PYY action involves vagal cholinergic-mediated CGRP/NO protective mechanisms.

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