Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P21817 (RyR1)
 1,154 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The importance of an intracellular calcium content increase to obtain cholinergic antinociception was demonstrated. The physiological and pathological role of ryanodine receptors (RyRs), receptors involved in the mobilization of intracellular calcium stores, at the CNS level is poorly understood. The aim of the present study was, therefore, to investigate the role of supraspinal endoplasmic type 1, 2 and 3 RyR subtypes in muscarinic antinociception in conditions of acute thermal (hotplate test) and inflammatory (abdominal constriction test) pain. In the absence of isoform selective RyR antagonists, types 1, 2 and 3 RyR knockdown mice were obtained. Western blotting experiments were performed to quantify the RyR isoform protein levels in knockdown mice demonstrating a selective protein level reduction in knockdown animals. I.c.v. pretreatment with an antisense oligonucleotide (aODN) against type 1 or type 3 RyR prevented cholinergic antinociception in the hotplate test shifting to the right of the physostigmine dose-response curve. This antagonistic effect disappeared 7 days after the end of the aODN administration. Conversely, the physostigmine analgesia remained unmodified in type 2 RyR knockdown mice. Similar results were obtained in the abdominal constriction test. Mice undergoing aODN treatments showed neither alteration of animals' gross behavior nor locomotor impairment (rota-rod and hole board tests). These results elucidate the intracellular mechanism underlying muscarinic antinociception. A selective involvement of RyR1 and RyR3 in supraspinal muscarinic analgesia was demonstrated whereas RyR2 appears not to play an essential role in acute thermal and inflammatory pain.
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PMID:Type 1 and type 3 ryanodine receptors are selectively involved in muscarinic antinociception in mice: an antisense study. 1840 25

The administration of the ryanodine receptor (RyR) agonist 4-Cmc (0.003-9 nmol per mouse intracerebroventricularly [i.c.v.]) ameliorated memory functions, whereas the RyR antagonist ryanodine (0.0001-1 nmol per mouse i.c.v.) induced amnesia in the mouse passive avoidance test. The role of the type 1, 2, and 3 RyR isoforms in memory processes was then evaluated by inhibiting the expression of the three RyR proteins in the mouse brain. A selective knockdown of the RyR isoforms was obtained by the i.c.v. administration of antisense oligonucleotides (aODNs) complementary to the sequence of RyR1, RyR2 and RyR3 proteins, as demonstrated by immunoblotting experiments. RyR1 (5-9 nmol per mouse i.c.v.) knockdown mice did not show any memory dysfunction. Conversely, RyR2 (1-7 nmol per mouse i.c.v.) and RyR3 (1-7 nmol per mouse i.c.v.) knockdown animals showed an impairment of memory processes. This detrimental effect was temporary and reversible, disappearing 7 d after the end of the aODN treatment. At the highest effective doses, none of the compounds used impaired motor coordination, as revealed by the rota rod test, nor modified spontaneous mobility and inspection activity, as revealed by the hole-board test. In conclusion, the lack of any involvement of cerebral RyR1 was demonstrated. These findings also showed the involvement of type 2 and type 3 RyR in the modulation of memory functions identifying these cerebral RyR isoforms as critical targets underlying memory processes.
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PMID:Different involvement of type 1, 2, and 3 ryanodine receptors in memory processes. 1844 Dec 89