A review of central 5-HT receptors and their function

https://www.suscch.eu/e107_files/public/Aorta/Guidelines_for_the_Diagnosis_and_Management_of_Patients_with_Thoracic_Aortic_Disease,_2010.pdf

2010 ACCF/AHA/AATS/ACR/ASA/SCA/SCAI/SIR/STS/SVM Guidelines for the Diagnosis and Management of Patients With Thoracic Aortic Disease

Mitochondria play a central role in the survival and death of neurons. The detailed bioenergetic mechanisms by which isolated mitochondria generate ATP, sequester Ca2+, generate reactive oxygen species, and undergo Ca2+-dependent permeabilization of their inner membrane are currently being applied to the function of mitochondria in situ within neurons under physiological and pathophysiological conditions. Here we review the functional bioenergetics of isolated mitochondria, with emphasis on the chemiosmotic proton circuit and the application (and occasional misapplication) of these principles to intact neurons. Mitochondria play an integral role in both necrotic and apoptotic neuronal cell death, and the bioenergetic principles underlying current studies are reviewed.

https://www.physiology.org/doi/pdf/10.1152/physrev.2000.80.1.315

Mitochondria and Neuronal Survival

A stereotaxic atlas of the rat brain

D1 and D2 dopamine-receptor modulation of striatal glutamatergic signaling in striatal medium spiny neurons

Noradrenaline inhibition of acetylcholine release from guinea-pig brain

Reciprocal dopamine-glutamate modulation of release in the basal ganglia.

Glutamate antagonists prevent morphine withdrawal in mice and guinea pigs

1
The newly discovered neuropeptide nociceptin (NC) has recently been reported to be the endogenous ligand of the opioid-like orphan receptor. Despite its structural similarity to opioids, when injected intracerebroventricularly (i.c.v.) in the mouse, NC exerts a direct hyperalgesic effect and reverses opioid-induced analgesia. In the present investigation, these two effects of NC were evaluated under the same experimental conditions; in addition, a pharmacological characterization of the receptor mediating these central effects of NC was attempted.

2
NC caused a dose dependent (0.1–10 nmol/mouse), naloxone-insensitive reduction of tail withdrawal latency with a maximal effect of about 50% of the reaction time observed in saline injected mice. In the same range of doses, NC inhibited morphine (1 nmol/mouse) induced analgesia.

3
The effects of the natural peptide were mimicked by NCNH2 and NC(1–13)NH2 (all tested at 1 nmol/mouse) while 1 nmol NC(1–9)NH2 was found to be inactive either in reducing tail withdrawal latency or in preventing morphine analgesia.

4
[Phe1ψ(CH2-NH)Gly2]NC(1–13)NH2 ([F/G]NC(1–13)NH2), which has been shown to antagonize NC effects in the mouse vas deferens, acted as an agonist, mimicking NC effects in both the experimental paradigms. In addition, when NC and [F/G]NC(1–13)NH2 were given together, their effects were additive.

5
These results demonstrate that both the direct hyperalgesic action and the anti-morphine effect of NC can be studied under the same experimental conditions in the mouse tail withdrawal assay. Moreover, the pharmacological characterization of the NC functional site responsible for these actions compared with the peripherally active site, indicates the existence of important differences between peripheral and central NC receptors.





British Journal of Pharmacology (1998) 125, 373–378; doi:10.1038/sj.bjp.0702087

/pdf/pharmacological-characterization-of-the-nociceptin-receptor-2g1f29b8zc.pdf

Pharmacological characterization of the nociceptin receptor mediating hyperalgesia in the mouse tail withdrawal assay.

1. The influence of 5-hydroxytryptamine1A (5-HT1A), 5-HT2 and 5-HT3 agonists and antagonists on acetylcholine (ACh) release from the cerebral cortex was studied in freely moving guinea-pigs. 2. 8-Hydroxy-2-(di-n-propylamino)tetralin (8-OH-DPAT, 0.01-1 mg kg-1, s.c.) caused the 5-HT syndrome and dose-dependently increased ACh release. Ru 24969 (1-10 mg kg-1, s.c.) shared the same effects, but it was less potent. (-)-Propranolol (5 mg kg-1) and metitepine (2 mg kg-1) prevented these behavioural and neurochemical responses. 3. (+/-)-1(4-Iodo-2,5-dimethoxyphenyl)2-aminopropane (DOI) up to 2 mg kg-1 did not modify ACh release and ketanserin (0.5 mg kg-1) was ineffective on 5-HT-induced changes of ACh outflow. 4. 2-Methyl-5-HT (500 micrograms, i.c.v.) and 5-HT (500 micrograms, i.c.v.) plus metitepine (2 mg kg-1, s.c.) inhibited the gross behaviour and ACh release. ICS 205-930 (0.5 mg kg-1) prevented these responses. 5. 2-Methyl-5-HT, up to 10 mumols 1(-1), and 8-OH-DPAT, up to 0.1 mumols 1(-1), (like 5-HT) did not change [3H]-choline efflux from cerebral cortex slices. 6. These results suggest that exogenous 5-HT and related selective agonists modulate guinea-pig cortical cholinergic structures through 5-HT1A and 5-HT3 receptors. The stimulation of 5-HT1A autoreceptors may lead to disinhibition of the cholinergic cells, tonically inhibited by the tryptaminergic control. Conversely, the stimulation of 5-HT3 receptors inhibits ACh release, possibly through an interneurone. No direct 5-HT modulation of the cholinergic nerve endings was found.

Lorenzo Beani

Papers

Noradrenaline inhibition of acetylcholine release from guinea-pig brain

Reciprocal dopamine-glutamate modulation of release in the basal ganglia.

Glutamate antagonists prevent morphine withdrawal in mice and guinea pigs

Pharmacological characterization of the nociceptin receptor mediating hyperalgesia in the mouse tail withdrawal assay.

5-HT1A agonists increase and 5-HT3 agonists decrease acetylcholine efflux from the cerebral cortex of freely-moving guinea-pigs.