Disease relevance of C10128

• Betel nuts, arecaidine, and oral cancer [1].
• Responses to pressure-applied isoguvacine, a GABAA receptor agonist, were reversibly depressed by anoxia, again because of a positive shift in reversal potential and decrease in conductance [2].
• Pre-perifusion of the pituitaries with pertussis toxin did not change the TSH response to TRH but completely inhibited the isoguvacine potentiation of the response [3].
• Fibroblasts cultured in vitro from normal buccal tissue and from tissue from oral submucous fibrosis (OSF) associated with betel-nut chewing showed no significant difference in their rates of proliferation in culture, nor in the rate at which they hydrolysed the betel nut alkaloid arecoline to arecaidine [4].

Psychiatry related information on C10128

• However, arecaidine, at the same i.c.v. doses, was able to reduce the pain threshold in the hot-plate and paw pressure tests.(ABSTRACT TRUNCATED AT 250 WORDS)[5]
• As tertiary arecaidine and isoarecaidine esters easily penetrate the blood-brain barrier, they might also stimulate central M1 receptors and thus become lead compounds in the search for an effective drug treatment of Alzheimer's disease [6].

High impact information on C10128

• Acetylcholine- and arecaidine propargyl ester-induced 6-keto-PGF1 alpha synthesis and cGMP formation in endothelial cells were attenuated by atropine, AF-DX 116 (M2 antagonist), and hexahydrosiladifenidol (M3 antagonist) but not by pirenzepine (M1 antagonist) [7].
• Employing this technique, we found that the GABAA agonists, muscimol, isoguvacine, 4,5,6,7-tetrahydroisoxazolo(5,4-C)pyridine-3-ol, and 3-amino-1-propane sulfonate, all produced a concentration-dependent increase in 36Cl- influx, but baclofen, a GABAB agonist, failed to alter 36Cl- flux [8].
• Either isoguvacine (a GABA(A) receptor agonist) or kynurenic acid (a non-selective ionotropic glutamate receptor antagonist) microinjected bilaterally into the paraventricular nucleus (PVN) attenuated the increase in LSNA induced by the hyperosmotic stimulus (control: 25 +/- 2%; after isoguvacine: 7 +/- 2%; after kynurenic: 8 +/- 3%) [9].
• In the formalin model of orofacial nociception in rats, a peri-oral co-injection of the M2 agonist arecaidine dose-dependently inhibited phase 2 nocifensive behavior up to approximately 50% at 5 nmol [10].
• Control experiments using a GABAA receptor agonist, isoguvacine, indicated that both components of the baroreflex (parasympathetic and sympathetic) could be blocked from the NTS injection site [11].

Biological context of C10128

• GABAB binding sites were localized using [3H]GABA in the presence of a saturating concentration of isoguvacine, a selective GABAA receptor agonist, to displace [3H]GABA bound to GABAA receptor sites [12].
• However, in marked and unexpected contrast, application of GABA and isoguvacine facilitated or triggered milk-ejection reflex bursting activity whereas GABAA antagonists interrupted this reflex activity [13].
• Isoguvacine (2.5 X 10(-5) M) did not affect action potential duration [14].
• Structure-activity relationships of new analogues of arecaidine propargyl ester at muscarinic M1 and M2 receptor subtypes [15].
• What role, if any, that is played by these uncommon metabolites in the toxicology of arecoline and arecaidine is not known [16].

Anatomical context of C10128

• Acetylcholine and arecaidine propargyl ester, a selective M2 agonist, produced a dose-dependent increase in 6-keto-PGF1 alpha output and cGMP formation in confluent endothelial cells but not in confluent vascular smooth muscle cells [7].
• Does uptake limit the actions of GABA agonists in vivo? Experiments with muscimol, isoguvacine and THIP in cat spinal cord [17].
• 2. Interneurons and pyramidal cells from P2-5 slices loaded with fluo-3 AM responded by an increase in [Ca2+]i to isoguvacine and to glutamate, in contrast to cells from P12-13 slices which responded to glutamate but not to isoguvacine [18].
• 2. The arecaidine 2-butynyl and 2-pentynyl esters were approximately equipotent with APE at M1 and M2 receptors, whereas the 2-hexynyl derivative was found to be less potent than APE in atria (-log EC50 = 6.80) and ileum (-log EC50 = 6.70) by about one order of magnitude [15].
• Likewise, isoguvacine (10(-5) to 10(-4) M) reduced amplitudes (-26.7% to -37.5%) and increased latencies (+11.2% and +24.0%) of cuneate-gracilis fasciculi responses but had little or no effect on corticospinal tract response amplitudes (-6.2% to -3.8%) or latencies (-0.8% to +1.5%) [19].

Associations of C10128 with other chemical compounds

• Both GABA and baclofen, but not isoguvacine, altered beta AR agonist binding by increasing the affinity of both the low- and high-affinity binding sites and by increasing the proportion of low-affinity receptors [20].
• Two different recombinant GABAA receptors (alpha 1 beta 3 and alpha 1 beta 3 gamma 2) were compared by measuring the relaxation of whole-cell currents during the application of GABA, isoguvacine or taurine [21].
• A metabolomic approach to the metabolism of the areca nut alkaloids arecoline and arecaidine in the mouse [16].
• The EC(so) values for GABA and its analogues isoguvacine, muscimol, isonipecotic acid and 3-amino sulphonic acid on the RDL(ad) homomeric receptor differed from those previously described for RDL(ac) and DRC17-1-2 receptors [22].
• The areca alkaloids comprise arecoline, arecaidine, guvacoline, and guvacine [16].

Gene context of C10128

• GABA or GABA(A) agonist isoguvacine treatment resulted in increased or decreased levels of several mRNAs, including transcription factors (c-fos, hsf-1, egr-1) and cell cycle-associated genes (Cdk2, cyclin D1) [23].
• Isoguvacine (EC50 approximately to 10 microM) induced biphasic relaxation for both alpha 1 beta 3 and alpha 1 beta 3 gamma 2 subunit receptors (tau 1 = 288.6 +/- 43.3 and 167 +/- 15 ms, and tau 2 = 8.0 +/- 1.9 and 4.4 +/- 0.4 S, respectively, for each subunit combination) [21].
• In contrast, the GABA(A) receptor agonists 3APS and isoguvacine (10(-5) M each) did not modify endozepine release [24].
• When neurointermediate lobes were treated for 3 days, inhibition of POMC biosynthesis by NPY was maintained, and inhibition by apomorphine was even stronger, whereas isoguvacine gave an inhibition of 52%, and baclofen produced 34% inhibition [25].
• The GABAA agonist, isoguvacine (10-100 microM), did not reduce SP release but, if anything, tended to increase SP release [26].

Analytical, diagnostic and therapeutic context of C10128

• 2. In the whole-cell recording (WCR) configuration inward Ca2+ currents triggered before and/or during the application of isoguvacine (100 microM), did not inhibit the GABAA receptor-mediated response [27].
• 3. Receptor autoradiography with [(3)H]-GABA in the presence of isoguvacine, and quantitative densitometric analysis were used to investigate GABA(B) receptor expression (B(max)) and affinity (K(D)) in 11 HS samples and eight controls [28].
• Subsequent isoguvacine microinjections at the same loci abolished PI-motor or laryngeal constrictor activity, triggered apneusis and established a variable and decreased breathing frequency [29].
• However, measurements of cerebellar GABAA receptor mRNAs for the alpha 1, beta 2L, beta 2S, beta 4, gamma 1, gamma 2L, and gamma 2S subunits by reverse transcriptase-polymerase chain reaction (RT-PCR) revealed no significant alterations by isoguvacine administration [30].
• We have developed a new ion-pairing reversed-phase high-performance liquid chromatographic (HPLC) method for the determination of arecoline in saliva, using arecaidine (1,2,5,6-tetrahydro-1-methylnicotinic acid) as an internal standard [31].

References