THE ROLE OF BRAIN STEM MUSCARINIC RECEPTORS IN THE REGULATION OF BREATHING

1996 ◽  
Author(s):  
Βασιλική Μάλλιου

ΧΟΛΙΝΕΡΓΙΚΟΙ ΜΗΧΑΝΙΣΜΟΙ ΠΑΙΖΟΥΝ ΣΗΜΑΝΤΙΚΟ ΡΟΛΟ ΣΤΟΝ ΕΛΕΓΧΟ ΤΗΣ ΑΝΑΠΝΟΗΣ, ΑΛΛΑ Η ΚΑΤΑΝΟΜΗ ΤΩΝ ΜΟΥΣΚΑΡΙΝΙΚΩΝ ΧΟΛΙΝΕΡΓΙΚΩΝ ΥΠΟΔΟΧΕΩΝ ΔΕΝ ΕΧΟΥΝ ΧΑΡΤΟΓΡΑΦΗΘΕΙ ΣΤΑ ΑΝΑΠΝΕΥΣΤΙΚΑ ΚΕΝΤΡΑ ΤΟΥ ΣΤΕΛΕΧΟΥ ΤΟΥ ΕΓΚΕΦΑΛΟΥ. ΤΟ ΠΡΩΤΟ ΜΕΡΟΣ ΤΗΣ ΠΑΡΟΥΣΑΣ ΕΡΓΑΣΙΑΣ ΕΞΕΤΑΣΕ ΤΗΝ ΥΠΟΘΕΣΗ ΟΤΙ ΥΠΑΡΧΕΙ ΕΤΕΡΟΓΕΝΗ ΚΑΤΑΝΟΜΗ MACHR ΥΠΟΔΟΧΕΩΝ ΣΤΑ ΑΝΑΠΝΕΥΣΤΙΚΑ ΚΕΝΤΡΑ. ΧΡΗΣΙΜΟΠΟΙΗΘΗΚΕ Η ΜΕΘΟΔΟΣ IN VITRO AUTORADIOGRAPHY ΓΙΑΤΗΝ ΠΟΣΟΤΙΚΗ ΚΑΙ ΠΟΙΟΤΙΚΗ ΚΑΤΑΝΟΜΗ ΤΩΝ ΥΠΟΔΟΧΕΩΝ ΣΤΑ ΑΝΑΠΝΕΥΣΤΙΚΑ ΚΕΝΤΡΑ. Η ΔΙΑΤΡΙΒΗ ΕΔΕΙΞΕ ΓΙΑ ΠΡΩΤΗ ΦΟΡΑ ΟΤΙ ΣΤΑ ΑΝΑΠΝΕΥΣΤΙΚΑ ΚΕΝΤΡΑ ΤΟΥ ΕΓΚΕΦΑΛΟΥ ΥΠΑΡΧΕΙ ΕΤΕΡΟΓΕΝΗ ΚΑΤΑΝΟΜΗ MACHR ΥΠΟΔΟΧΕΩΝ. ΕΤΣΙ ΣΤΑ ΑΠΟΤΕΛΕΣΜΑΤΑ ΤΗΣ ΠΑΡΟΥΣΑΣ ΕΡΓΑΣΙΑΣ ΕΙΝΑΙ ΟΥΣΙΑΣΤΙΚΟ ΠΡΩΤΟ ΒΗΜΑ ΓΙΑ ΜΕΛΛΟΝΤΙΚΕΣ ΕΡΓΑΣΙΕΣ ΜΕ ΣΤΟΧΟ ΝΑ ΔΙΕΥΚΡΙΝΙΣΤΕΙ Ο ΛΕΙΤΟΥΡΓΙΚΟΣ ΡΟΛΟΣ ΤΩΝ MACHR ΥΠΟΔΟΧΕΩΝ ΤΟΥ ΣΤΕΛΕΧΟΥ ΣΤΟΝ ΕΛΕΓΧΟ ΤΗΣ ΑΝΑΠΝΟΗΣ. ΤΟ ΔΕΥΤΕΡΟ ΜΕΡΟΣ ΤΗΣ ΔΙΑΤΡΙΒΗΣ ΕΞΕΤΑΣΕ ΤΗΝ ΔΡΑΣΗ ΤΟΥ ΜΟΥΣΚΑΡΙΝΙΚΟΥ ΑΓΩΝΙΣΤΗ BETH ΚΑΙ ΤΩΝ ΜΟΥΣΚΑΡΙΝΙΚΩΝ ΑΝΤΑΓΩΝΙΣΤΩΝ 4-DAMP ΚΑΙ METHATRAMINE ΣΤΗΝ ΑΝΑΠΝΕΥΣΤΙΚΗ ΣΥΧΝΟΤΗΤΑ (AL) ΚΑΤΑ ΤΗ ΔΙΑΡΚΕΙΑ NREM ΚΑΙ REM ΥΠΝΟΥ. Η ΕΡΓΑΣΙΑ ΕΔΕΙΞΕ ΟΤΙ Η BETH ΣΤΟ MPRF ΤΟΥ ΣΤΕΛΕΧΟΥ ΠΡΟΚΑΛΕΙ ΜΕΙΩΣΗ ΤΗΣ ΑΣ (P < 0.05) ΚΑΤΑ NREMΚΑΙ REM ΥΠΝΟΥ. ΜΙΚΡΟΕΓΧΥΣΕΙΣ 4-DAMP ΚΑΙ METH ΧΡΗΣΙΜΟΠΟΙΗΘΗΚΑΝ ΓΙΑ ΤΗΝ ΕΞΕΤΑΣΗΤΗΣ ΥΠΟΘΕΣΗΣ ΟΤΙ Η ΜΕΙΩΣΗ ΤΗΣ ΑΣ ΔΕΝ ΜΠΟΡΕΙ ΝΑ ΞΕΧΩΡΙΣΤΕΙ ΑΠΟ ΤΟ ΣΤΑΔΙΟ ΕΓΡΗΓΟΡΣΗΣ. Η ΕΡΓΑΣΙΑ ΑΥΤΗ ΕΔΕΙΞΕ ΓΙΑ ΠΡΩΤΗ ΦΟΡΑ ΟΤΙ ΟΙ ΜΟΥΣΚΑΡΙΝΙΚΟΙ ΑΝΤΑΓΩΝΙΣΤΕΣ 4-DAMP ΚΑΙ METH ΔΕΝ ΕΜΠΟΔΙΣΑΝ ΤΗΝ ΜΕΙΩΣΗ ΤΗΣ ΑΣ ΠΟΥ ΣΥΝΟΔΕΥΕΙ ΤΟ ΣΤΑΔΙΟ ΕΓΡΗΓΟΡΣΗΣ.

1997 ◽  
Vol 120 (8) ◽  
pp. 1409-1418 ◽  
Author(s):  
S. S. Hegde ◽  
A. Choppin ◽  
D. Bonhaus ◽  
S. Briaud ◽  
M. Loeb ◽  
...  

2005 ◽  
Vol 93 (4) ◽  
pp. 2127-2141 ◽  
Author(s):  
Frédéric Brocard ◽  
Cédric Bardy ◽  
Réjean Dubuc

Substance P initiates locomotion when injected in the brain stem of mammals. This study examined the possible role of this peptide on the supraspinal locomotor command system in lampreys. Substance P was bath applied or locally injected into an in vitro isolated brain stem, and the effects of the drug were examined on reticulospinal cells and on the occurrence of swimming in a semi-intact preparation. Bath applications of substance P induced sustained depolarizations occurring rhythmically in intracellularly recorded reticulospinal cells. Spiking activity was superimposed on the depolarizations and swimming was induced. The sustained depolarizations were abolished by tetrodotoxin, and substance P did not affect the membrane resistance of reticulospinal cells nor their firing properties, suggesting that it did not directly effect reticulospinal cells. To establish where the effects were exerted, successive lesions of the brain stem were made as well as local applications of the drug in the brain stem. Removing the mesencephalon abolished the sustained depolarizations, whereas large ejections of the drug in the mesencephalon excited reticulospinal cells and elicited bouts of swimming. More local injections into the mesencephalic locomotor region (MLR) also elicited swimming. After an injection of substance P, the current threshold needed to induce locomotion by MLR stimulation was decreased, and the size of the postsynaptic responses of reticulospinal cells to MLR stimulation was increased. Substance P also reduced the frequency of miniature spontaneous postsynaptic currents in reticulospinal cells. Taken together, these results suggest that substance P plays a neuromodulatory role on the brain stem locomotor networks of lampreys.


2000 ◽  
Vol 131 (7) ◽  
pp. 1482-1488 ◽  
Author(s):  
Tomonori Yamanishi ◽  
Christopher R Chapple ◽  
Kosaku Yasuda ◽  
Russell Chess-Williams

1997 ◽  
Vol 273 (3) ◽  
pp. L531-L536 ◽  
Author(s):  
M. Jakupaj ◽  
R. J. Martin ◽  
I. A. Dreshaj ◽  
C. F. Potter ◽  
M. A. Haxhiu ◽  
...  

We sought to characterize the role of endogenous nitric oxide (NO) released from airway epithelium in attenuating tracheal smooth muscle (TSM) contraction induced by exposure to acetylcholine (ACh). Organ bath experiments were performed on TSM from young pigs of three ages (3-7 days, 2-3 wk, and 3 mo). Concentration-response curves to cumulative doses of ACh (10(-8) to 10(-4) M) were generated before and after addition of the NO synthase blocker N omega-nitro-L-arginine methyl ester (L-NAME). L-NAME caused a significant increase in cholinergic sensitivity (decrease in 50% effective dose) at 3-7 days and 2-3 wk but not 3 mo. Maximum responses to ACh increased after L-NAME at all three ages. Removal of tracheal epithelium caused a significant increase in sensitivity to ACh at all ages, which progressively declined with advancing age. In the absence of epithelium, L-NAME no longer influenced contractile responses to ACh. Density of M3 muscarinic receptors in tracheal epithelium was upregulated in the youngest piglets. We conclude that, under in vitro conditions, release of endogenous NO opposes cholinergically induced contraction of piglet TSM. This phenomenon diminishes with advancing postnatal age, requires an intact airway epithelium, and correlates with upregulation of M3 muscarinic receptors in airway epithelium. We speculate that NO may play a useful role in attenuating cholinergically mediated airway smooth muscle contraction in early life when pulmonary function is characterized by high airway resistance.


2003 ◽  
Vol 4 (3) ◽  
pp. 218-231 ◽  
Author(s):  
Joan A. Masters ◽  
Joanne S. Stevenson

Uncertainty about the mechanism of alcohol-mediated arrhythmogenesis and the effect of alcohol use on arrhythmic risk among older adults is an increasing concern in light of population aging and recent reports that moderate alcohol consumption may protect older adults against coronary artery disease. In this review, a theoretical model of the role of brain stem nuclei in alcohol-mediated arrhythmogenesis in older adults is developed. The model is based on the hypothesis that the effects of alcohol on central autonomic pathways of cardiac control may alter the threshold for alcohol-mediated arrhythmogenesis among older adults. Findings from multiple lines of research including cellular, electrophysiological, epidemiological, experimental, and clinical studies in human, animal, and in vitro models were synthesized in developing the model. Suggestions for future research on the topic of alcohol-mediated arrhythmogenesis in older adults are offered.


1995 ◽  
Vol 268 (6) ◽  
pp. L941-L949 ◽  
Author(s):  
V. J. Mallios ◽  
R. Lydic ◽  
H. A. Baghdoyan

Cholinergic mechanisms are known to play a key role in the regulation of breathing, but the distribution of muscarinic receptor (mAChR) subtypes has not been localized within brain stem respiratory nuclei. This study examined the hypothesis that mAChR subtypes are heterogeneously distributed across brain stem nuclei that control breathing. With the use of in vitro receptor autoradiography, the results provide the first selective labeling and quantitative mapping of M1, M2, and M3 mAChR subtypes in cat brain stem regions known to regulate breathing. Among brain stem nuclei known to contain respiratory-related neurons, the greatest amount of mAChR binding was measured in the lateral and medial parabrachial nuclei and the lateral nucleus of the solitary tract. Fewer mAChRs were localized in nuclei comprising the ventral respiratory group (nucleus ambiguous, retrofacial nucleus) and ventral medulla (retrotrapezoid nucleus and ventrolateral medulla). The data provide an essential first step for future studies aiming to specify the regulatory role of mAChR subtypes within brain stem respiratory nuclei.


2020 ◽  
Vol 103 (6) ◽  
pp. 1238-1248
Author(s):  
Zheng Wang ◽  
Adoulaye Issotina Zibrila ◽  
Shuhua Liu ◽  
Gongxiao Zhao ◽  
Yubei Li ◽  
...  

Abstract Oxidative stress and apoptosis of trophoblasts are involved in preeclampsia (PE). Numerous studies have shown that acetylcholine (ACh), the principal vagal neurotransmitter, plays a crucial role in attenuating oxidative stress, inflammation, and apoptosis in a variety of human diseases. However, the role of ACh in PE management remains unclear. Here, we aimed to determine the effects of ACh on TNF-α-treated human primary trophoblast cells. Western blotting, CCK-8, DHE, TUNEL immunofluorescence staining, transwell assays, and wound-healing assays were performed to evaluate the role of ACh in vitro. We found that both TNF-α expression and the apoptotic index were higher in placentas from preeclamptic women than in normal placentas. TNF-α enhanced oxidative stress and increased the number of TUNEL-positive nuclei, Bax/Bcl-2 ratio, and the cleaved caspase-3/caspase-3 ratio while decreasing cell viability in primary human trophoblast cells. TNF-α promoted cell migration and invasion. PDTC, a selective NF-κB inhibitor, significantly blunted TNF-α-induced effects. ACh treatment attenuated oxidative stress and apoptosis while further promoting migration and invasion of TNF-α-treated primary trophoblast cells. The effects of ACh could be reversed by the muscarinic receptor antagonist atropine. Overall, our findings indicate that ACh significantly ameliorates TNF-α-induced oxidative stress and apoptosis of human primary trophoblast cells via muscarinic receptors. This is the first time that the improvement of vagal activity served as a therapeutic strategy for PE-like trophoblasts, suggesting its potential value in clinical practice.


2017 ◽  
Vol 115 ◽  
pp. 387-392 ◽  
Author(s):  
Alessandro Menozzi ◽  
Cristina Pozzoli ◽  
Enzo Poli ◽  
Giada Bontempi ◽  
Paolo Serventi ◽  
...  

Sign in / Sign up

Export Citation Format

Share Document