Disease relevance of Oxytremorine

• GRK5-KO mice exhibited mild spontaneous hypothermia as well as pronounced behavioral supersensitivity upon challenge with the nonselective muscarinic agonist oxotremorine [1].
• From the rate of accumulation of serotonin in the ganglion after the administration of the monoamine oxidase inhibitor pargyline, it appears that the rate of formation of serotonin is increased after oxotremorine treatment [2].
• They underwent subsequent tests with saline solution, propranolol (1 mg/kg body weight), methacholine (0.5 microgram/kg per min) and oxotremorine (8 micrograms/kg) [3].
• PDBu-stimulated cyclic AMP accumulation was unaffected by pretreatment of cells with pertussis toxin or the inhibitory muscarinic agonist, oxotremorine [4].
• TA3 antagonized apomorphine- and oxotremorine-induced hypothermia, potentiated yohimbine-induced toxicity and L-5-hydroxy-tryptophan-induced head twitches, but did not affect forced swimming-induced immobility or reserpine-induced hypothermia [5].

Psychiatry related information on Oxytremorine

• Induction of depression with oxotremorine in patients with Alzheimer's disease [6].
• In contrast, the in vivo effects of oxotremorine (hypothermia and antinociception) were markedly enhanced in aged rats, whereas scopolamine-induced locomotor activity was reduced [7].
• In narcoleptic canines, bilateral perfusion with oxotremorine (M2 muscarinic) (10(-5)-10(-3) M) in the pontine reticular formation produced a dose-dependent increase in cataplexy, which reached complete muscle atonia (status cataplecticus) during the highest concentration [8].
• D-(R)-2-partially attenuated amphetamine-induced stereotyped behavior, whereas D-(R)-4 antagonized oxotremorine-induced tremors [9].
• 6-OHDA reduced the reaction time of mice to nociceptive stimulus (hot plate) and attenuated the antinociceptive action of oxotremorine [10].

High impact information on Oxytremorine

• In parallel studies, oxotremorine and bethanechol, muscarinic agonists, and racemic quinuclidinyl benzilate altered short-circuit current in rat colon in vitro in concentrations that were in good agreement with the concentrations that inhibited L-[benzilic-4,4-3H]quinuclidinyl benzilate binding to the crude membrane preparation [11].
• OXO enhanced retention when infused into the hippocampus after context, but not footshock, training [12].
• Treatment of sarcolemmal membranes with IAP attenuated the ability of oxotremorine to both stimulate high-affinity GTPase activity and inhibit adenylate cyclase activity [13].
• Isolated smooth muscle tissues of the rabbit saphenous artery precontracted with norepinephrine (NE) were relaxed by acetylcholine (ACh, greater than 10(-7) M) or oxotremorine (greater than 10(-7) M), through the activation of muscarinic receptors, only when the endothelial cells were intact [14].
• Oxotremorine (up to 10(-5) M) did not alter the membrane potential in the presence or absence of the endothelium [14].

Chemical compound and disease context of Oxytremorine

• Some tertiary antimuscarinic amines related to oxotremorine were compared with atropine and scopolamine for their ability to block physostigmine-induced hypertension and acetylcholine-induced hypotension in rats [15].
• In narcoleptic canines, carbachol and oxotremorine (10(-5)-10(-3) M), but not McN-A-343 or nicotine (10(-4)-10(-3) M), produced a dose-dependent increase in cataplexy [16].
• Effects of scopolamine, pilocarpine, and oxotremorine on the exploratory behavior of two psychogenetically selected lines of rats in a complex maze [17].
• 4 Pretreatment with propranolol (5 mg/kg s.c.) prevented the lactic acidosis and fall in pH but did not alter the respiratory stimulation induced by oxotremorine [18].
• The oxotremorine-induced inhibition was attenuated by N-ethylmaleimide (3 x 10(-5) M for 50 min), but was not affected by pertussis toxin pretreatment (10 micrograms/rat, for 4 days) [19].

Biological context of Oxytremorine

• The stimulation of muscarinic receptors with oxotremorine provoked a dramatic alteration of m2R compartmentalization, including endocytosis with a decrease of the density of m2R at the membrane (-63%) and an increase of those associated with endosomes (+86%) in perikarya [20].
• With the 3 full agonists oxotremorine, muscarine, and carbamylcholine, the receptor population could be divided into two classes of binding sites: a minor one (15%) with high affinity (KD = 20-35 nM) and a major one (85%) with low affinity (KD = 3-65 microM) [21].
• In testing the possibility that VGCC may be functionally coupled to mAChR in SCC cell lines, we found that depolarization-dependent Ca2+ influx was inhibited by carbachol (IC50 = 0.78 microM) and oxotremorine (IC50 = 0.69 microM) [22].
• The oxotremorine-induced decrease in phosphorylation was accompanied by a decrease in molecular weight [23].
• Propranolol and oxotremorine significantly reduced heart rate compared with saline solution, whereas methacholine did not [3].

Anatomical context of Oxytremorine

• The lowest behaviorally effective dose, 0.5 microgram OXO, did not influence WM performance when infused into the lateral ventricles (intracerebroventricularly) of either 22MO or 4MO rats [24].
• Systemic administration of the muscarinic agonist oxotremorine (OXO, 0.1 to 1.0 mg/kg, i.p.) increased LCGU in the neocortex, mesocortex, and paleocortex [25].
• (2) Stimulation of muscarinic receptor with oxotremorine provokes translocation of m4R from the membrane to endosomes in perikarya and dendrites of medium spiny neurons but has no influence on the localization of m4R in the cytoplasm of cholinergic cell bodies [26].
• Calcium current modulation by the muscarinic cholinergic agonist oxotremorine methiodide (oxo-M) was examined in sympathetic neurons from the superior cervical ganglion of the rat [27].
• The muscarinic effects of analogs of oxotremorine were compared on strips of the guinea pig ileum and urinary bladder [28].

Associations of Oxytremorine with other chemical compounds

• The phosphorylation of this protein was abolished by short term treatment of the isoproterenol-treated tissue with the muscarinic receptor agonist oxotremorine [23].
• Acetylcholine (100 pmol/L; human bronchi) or oxotremorine (1, 100, 10,000 nmol/L; rat trachea) did not affect the spontaneous histamine release [29].
• However, the rat striatal and N1E-115 M4 receptor differed in their binding of oxotremorine and pilocarpine, indicating that these two M4 systems were not pharmacologically identical.(ABSTRACT TRUNCATED AT 400 WORDS)[30]
• The interaction of a mustard analogue of oxotremorine, N-[4-(2-chloroethylmethylamino)-2-butynyl]-2-pyrrolidone (BM 123), with muscarinic receptors in the rat cerebral cortex was investigated using 3H-ligand-binding methods [31].
• The affinities of oxotremorine and arecoline were similar between the two cell lines [32].

Gene context of Oxytremorine

• In addition, dose-response curves were determined for antagonism of oxotremorine-induced salivation (mediated by M3 receptors) and tremor (mediated by non-M1 receptors) in mice [33].
• Oxotremorine-induced tremor was abolished only in the M2 knockout mice [34].
• Physiological response to the muscarinic agonists, oxotremorine (OXO) and pilocarpine, showed that AChE-/- mice were resistant to OXO-induced hypothermia, tremor, salivation, and analgesia, and to pilocarpine-induced seizures [35].
• We now report significantly greater inductions of c-fos, c-jun, jun-B, and Egr-1, but not jun-D, mRNA in the central nervous system (CNS) of LS versus SS mice after the intraperitoneal administration of oxotremorine [36].
• McN-A-343 (M1 muscarinic agonist) dose dependently stimulated GLP-1 secretion (to 252 +/- 50% of control at 1000 microM; P < 0.01), whereas oxotremorine (M3 agonist) had no effect [37].

Analytical, diagnostic and therapeutic context of Oxytremorine

• Using whole-cell patch-clamp techniques, which isolate the slow pathway, we found that the muscarinic agonist oxotremorine methiodide not only inhibits currents at positive potentials but enhances N-type current at negative potentials [38].
• After parasympathectomy, ventricular sarcolemma displayed significant increases in both basal and oxotremorine-stimulated GTPase activity [39].
• Intracerebroventricular (i.c.v.) pretreatment with antisense oligonucleotides (aODNs) against the alpha subunit of G(q) and G(11) proteins prevented the analgesia induced by physostigmine and oxotremorine [40].
• In control canines bilateral perfusion with oxotremorine (10(-5)-10(-3) M) did not produce any cataplectic attacks, but did produce muscle atonia after the highest concentration [8].
• After treatment of embryos in vivo with carbachol to decrease the reserve of spare receptors in the atria, oxotremorine could no longer elicit a significant negative chronotropic response under conditions in which carbachol was still effective [41].

References