Chapter 15 Prostaglandin system in the brain: sites of biosynthesis and sites of action under normal and hyperthermic states

Author(s):  
Kiyoshi Matsumura ◽  
Chunyu Cao ◽  
Yumiko Watanabe ◽  
Yasuyoshi Watanabe
2011 ◽  
Vol 91 (3) ◽  
pp. 1009-1022 ◽  
Author(s):  
Mansi Vithlani ◽  
Miho Terunuma ◽  
Stephen J. Moss

Inhibition in the adult mammalian central nervous system (CNS) is mediated by γ-aminobutyric acid (GABA). The fast inhibitory actions of GABA are mediated by GABA type A receptors (GABAARs); they mediate both phasic and tonic inhibition in the brain and are the principle sites of action for anticonvulsant, anxiolytic, and sedative-hypnotic agents that include benzodiazepines, barbiturates, neurosteroids, and some general anesthetics. GABAARs are heteropentameric ligand-gated ion channels that are found concentrated at inhibitory postsynaptic sites where they mediate phasic inhibition and at extrasynaptic sites where they mediate tonic inhibition. The efficacy of inhibition and thus neuronal excitability is critically dependent on the accumulation of specific GABAAR subtypes at inhibitory synapses. Here we evaluate how neurons control the number of GABAARs on the neuronal plasma membrane together with their selective stabilization at synaptic sites. We then go on to examine the impact that these processes have on the strength of synaptic inhibition and behavior.


1992 ◽  
Vol 70 (5) ◽  
pp. 772-772
Author(s):  
Alastair V. Ferguson

Since the recognition in the 1970s that peptides may play more diverse physiological roles than suggested by their original recognition as circulating hormones, there has been an explosion of information regarding the potential central nervous system actions of these substances. Pharmacological binding studies have described an extensive distribution of many different groups of peptidergic receptors suggesting potential sites of action for specific peptides within the brain. Many of these receptor localizations were found within the blood brain barrier indicating that these substances were released locally and perhaps acted as neurotransmitters. Over the years, experiments demonstrating physiological effects of locally administered peptides in regions where receptors for that molecule are localized have added credibility to such a hypothesis. The explosion of interest in the peptides as potential chemical messengers within the brain has since led to the description of multiple peptidergic neuronal systems within the brain. In addition, there are now many different reports of postsynaptic effects of exogenous administration of peptides on single neurons. Similarly, many studies have reported more broad-based physiological effects resulting from actions of peptides within the central nervous system.The manuscripts that follow summarize presentations in a symposium to examine the "Central Peptidergic Mechanisms in Autonomic Control," which was part of the program at the Canadian Federation of Biological Sciences annual meeting held at Queen's University in Kingston in July of 1991. The express purpose of this symposium in its inception was to provide a forum for consideration of the CNS actions of peptides in the context of a systems physiology approach. We hoped to consider our current knowledge of the roles of peptides in the brain as they relate to the control of specific physiological systems. Therefore rather than presenting a consideration of individual peptides, and each one's multitude of potential roles, the manuscripts presented in the following section have addressed what is known of central peptidergic involvement in the physiological control of reproductive function (W. K. Samson), cardiovascular regulation (A. V. Ferguson), thermoregulatory control (Q. J. Pittman), and drinking (M. Evered).I should like to take this opportunity to thank all who contributed to this symposium, in particular the speakers without whose cooperation it would not have been possible. I am also indebted to the sponsors of the symposium: Merck Frosst, Warner Lambert, Sandoz, the Canadian Physiological Society, and the Faculty of Medicine at Queen's University, whose generous support permitted such a highly qualified group of invited speakers to attend.


Author(s):  
P. L. R. Andrews ◽  
J. B. Messenger ◽  
E. M. Tansey

Various neurotransmitters were injected into the blood supplying the brain of Octopus vulgaris and the effects, particularly on the chromatophores, were observed. l-glutamate, GABA, dopamine, noradrenaline and octopamine caused expansion of the chromatophores and darkening of the skin; ACh caused retraction of the chromatophores and paling; 5HT caused differential expansion and retraction: mottling. These responses, which are neurally mediated, were particularly well defined for ACh and 5HT and the effects of these drugs were studied in more detail. The paling effect of ACh was mimicked by nicotine but not muscarine and was partially antagonized by tubocurarine. The mottling induced by 5HT was transiently antagonized by methysergide maleate, as was ink-ejection and defaecation. Brain lesions to localize the sites of action of ACh and 5HT suggest that they act at the level of the sub-oesophageal lobes to control the chromatophores, but that 5 HT may act at the level of the optic lobe to control inking and defaecation. These results are related to the pharmacology and histochemistry of the cephalopod brain and to the organization of the chromatophore control system.


1986 ◽  
Vol 63 (1) ◽  
Author(s):  
H.D. Rees ◽  
R.W. Bonsall ◽  
R.P. Michael
Keyword(s):  

1976 ◽  
Vol 82 (4) ◽  
pp. 785-791 ◽  
Author(s):  
Shaul Feldman ◽  
Nissim Conforti

ABSTRACT In order to elucidate the mechanisms and the sites of action of the negative feedback of corticoids in the regulation of ACTH secretion, the effects of systemically administered dexamethasone on adrenocortical responses to ether stress were studied in intact rats and in 11 experimental groups. These included animals with partial anterior, anterolateral, posterolateral, posterior and small posterior deafferentations as well as bilateral lesions in the medial forebrain bundle (MFB), fasciculus longitudinalis dorsalis (FLD), medial and lateral midbrain reticular formation (MRF) and in the ventrolateral pons. In rats with posterior hypothalamic deafferentation the degree of the inhibitory effect of dexamethasone was much smaller than that in intact animals. In animals with lesions in the FLD and MRF, dexamethasone also produced a reduction in the suppression of the response, though the difference was not significant. Bilateral lesions in the MFB and MP have on the other hand very significantly enhanced the effect of the negative feedback of dexamethasone when compared to intact rats. These data would indicate that hypothalamic deafferentations and brain lesions may change the sensitivity of the hypothalamus for the feedback control of corticoids and that there exist two antagonistic systems, an inhibitory and a facilitatory, in the brain which mediate this effect.


1999 ◽  
Vol 13 (suppl a) ◽  
pp. 18A-25A ◽  
Author(s):  
Yvette Taché ◽  
Vicente Martinez ◽  
Mulugeta Million ◽  
Jean Rivier

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 CRF2receptors, while the anxiogenic and colonic motor responses may involve CRF1receptors. Hypersecretion of CRF in the brain may contribute to the pathophysiology of stress-related exacerbation of irritable bowel syndrome.


Neuroglia ◽  
2018 ◽  
Vol 1 (1) ◽  
pp. 176-187 ◽  
Author(s):  
Csilla Brasko ◽  
Arthur Butt

Inward rectifying potassium (Kir) channels comprise a large family with diverse biophysical properties. A predominant feature of central nervous system (CNS) glia is their expression of Kir4.1, which as homomers are weakly rectifying channels, but form strongly rectifying channels as heteromers with Kir2.1. However, the extent of Kir2.1 expression and their association with Kir4.1 in glia throughout the CNS is unclear. We have examined this in astrocytes and oligodendrocytes of the mouse optic nerve, a typical CNS white matter tract. Western blot and immunocytochemistry demonstrates that optic nerve astrocytes and oligodendrocytes express Kir2.1 and that it co-localises with Kir4.1. Co-immunoprecipitation analysis provided further evidence that Kir2.1 associate with Kir4.1 and, moreover, Kir2.1 expression was significantly reduced in optic nerves and brains from Kir4.1 knock-out mice. In addition, optic nerve glia express Kir5.1, which may associate with Kir2.1 to form silent channels. Immunocytochemical and co-immunoprecipitation analyses indicate that Kir2.1 associate with Kir5.1 in optic nerve glia, but not in the brain. The results provide evidence that astrocytes and oligodendrocytes may express heteromeric Kir2.1/Kir4.1 and Kir2.1/Kir5.1 channels, together with homomeric Kir2.1 and Kir4.1 channels. In astrocytes, expression of multiple Kir channels is the biophysical substrate for the uptake and redistribution of K+ released during neuronal electrical activity known as ‘potassium spatial buffering’. Our findings suggest a similar potential role for the diverse Kir channels expressed by oligodendrocytes, which by way of their myelin sheaths are intimately associated with the sites of action potential propagation and axonal K+ release.


2007 ◽  
Vol 292 (3) ◽  
pp. R1092-R1100 ◽  
Author(s):  
V. Baptista ◽  
K. N. Browning ◽  
R. A. Travagli

We have shown recently that cholecystokinin octapeptide (CCK-8s) increases glutamate release from nerve terminals onto neurons of the nucleus tractus solitarius pars centralis (cNTS). The effects of CCK on gastrointestinal-related functions have, however, been attributed almost exclusively to its paracrine action on vagal afferent fibers. Because it has been reported that systemic or perivagal capsaicin pretreatment abolishes the effects of CCK, the aim of the present work was to investigate the response of cNTS neurons to CCK-8s in vagally deafferented rats. In surgically deafferented rats, intraperitoneal administration of 1 or 3 μg/kg CCK-8s increased c-Fos expression in cNTS neurons (139 and 251% of control, respectively), suggesting that CCK-8s' effects are partially independent of vagal afferent fibers. Using whole cell patch-clamp techniques in thin brain stem slices, we observed that CCK-8s increased the frequency of spontaneous and miniature excitatory postsynaptic currents in 43% of the cNTS neurons via a presynaptic mechanism. In slices from deafferented rats, the percentage of cNTS neurons receiving glutamatergic inputs responding to CCK-8s decreased by ∼50%, further suggesting that central terminals of vagal afferent fibers are not the sole site for the action of CCK-8s in the brain stem. Taken together, our data suggest that the sites of action of CCK-8s include the brain stem, and in cNTS, the actions of CCK-8s are not restricted to vagal central terminals but that nonvagal synapses are also involved.


Endocrinology ◽  
2004 ◽  
Vol 145 (10) ◽  
pp. 4470-4479 ◽  
Author(s):  
Soon Lee ◽  
Daniel Selvage ◽  
Keith Hansen ◽  
Catherine Rivier

Abstract The peripheral injection of alcohol stimulates the activity of the hypothalamic-pituitary-adrenal (HPA) axis, but the ready penetration of this drug in most bodily compartments has made it difficult to identify its specific sites of action. Here we determined whether alcohol can directly influence the corticotropes. We first determined whether alcohol acted within the brain to stimulate neurons in the paraventricular nucleus (PVN) of the hypothalamus, which synthesizes corticotropin-releasing factor (CRF) and vasopressin (VP). To test this hypothesis, we injected alcohol intracerebroventricularly (icv; 5 μl of 200-proof; 86 μmol) and compared these results with those obtained after its ip administration (3.0 g/kg). Although not causing neuronal damage and not leading to detectable levels of the drug in the general circulation, icv alcohol significantly up-regulated PVN CRF heteronuclear RNA levels and increased plasma ACTH levels, a change comparable to the one observed in the ip model. To determine whether alcohol stimulated the corticotropes independently of CRF and/or VP, we injected the drug ip or icv and measured changes in anterior pituitary proopiomelanocortin (POMC) transcripts and ACTH release in the presence or absence of endogenous CRF and/or VP. Intracerebroventricular and ip alcohol significantly increased POMC primary transcript levels, measured by ribonuclease protection assay, over a time-course that corresponded to ACTH release. Both the POMC and the ACTH responses were completely abolished by removal of CRF and VP. Collectively, these results indicate that alcohol-induced activation of the corticotropes does not represent a direct influence of the drug on the pituitary but requires CRF and VP.


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