Inhibitory effect of strychnine on acetylcholine receptor activation in bovine adrenal medullary chromaffin cells

Kuijpers, Gemma A.J.; Vergara, Leoncio; Calvo, Soledad; Yadid, Gal

doi:10.1111/j.1476-5381.1994.tb17013.x

Cited by 17 publications

(14 citation statements)

References 45 publications

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“…The affinity sequence for strychnine action on AcChoRs was (10,13,20); a similar inhibition of the nicotine response by strychnine was found in chicken ciliary ganglion neurons (11).…”

Section: Discussionsupporting

confidence: 58%

“…They are activated by the neurotransmitter acetylcholine (AcCho), and they mediate fast synaptic transmission at the neuromuscular junction and throughout the vertebrate nervous system (2)(3)(4). Additionally, AcChoRs are regulated by a wide variety of substances (5,6), including strychnine, a selective antagonist of glycine-gated Cl Ϫ channels (7) that inhibits AcChoRs at the neuromuscular junction (8) and different types of neurons (9)(10)(11)(12)(13). Moreover, it appears that this inhibition depends on the subtype of nicotinic receptor involved.…”

mentioning

confidence: 99%

“…Moreover, it appears that this inhibition depends on the subtype of nicotinic receptor involved. For instance, in bovine adrenal chromaffin cells and rat hippocampal neurons, strychnine inhibits AcChoRs competitively whereas for ␣ 4 ␤ 2 -containing AcChoRs the inhibition is noncompetitive (10,13). Here, we report the effects of strychnine on muscle AcChoRs made up of ␣ 1 ␤ 1 ␥␦, ␣ 1 ␤ 1 ␥, or ␣ 1 ␤ 1 ␦ muscle subunits and on two subtypes of neuronal AcChoRs (␣ 2 ␤ 2 or ␣ 2 ␤ 4 ).…”

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confidence: 99%

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Modulation of nicotinic acetylcholine receptors by strychnine

Garcı́a-Colunga

Miledi²

1999

Proc. Natl. Acad. Sci. U.S.A.

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Strychnine, a potent and selective antagonist at glycine receptors, was found to inhibit muscle (␣ 1 ␤ 1 ␥␦, ␣ 1 ␤ 1 ␥, and ␣ 1 ␤ 1 ␦) and neuronal (␣ 2 ␤ 2 and ␣ 2 ␤ 4 ) nicotinic acetylcholine receptors (AcChoRs) expressed in Xenopus oocytes. Strychnine alone (up to 500 M) did not elicit membrane currents in oocytes expressing AcChoRs, but, when applied before, concomitantly, or during superfusion of acetylcholine (AcCho), it rapidly and reversibly inhibited the current elicited by AcCho (AcCho-current). Although in the three cases the AcCho-current was reduced to the same level, its recovery was slower when the oocytes were preincubated with strychnine. The amount of AcCho-current inhibition depended on the receptor subtype, and the order of blocking potency by strychnine was ␣ 1 ␤ 1 ␥␦ > ␣ 2 ␤ 4 > ␣ 2 ␤ 2 . With the three forms of drug application, the Hill coefficient was close to one, suggesting a single site for the receptor interaction with strychnine, and this interaction appears to be noncompetitive. The inhibitory effects on muscle AcChoRs were voltageindependent, and the apparent dissociation constant for AcCho was not appreciably changed by strychnine. In contrast, the inhibitory effects on neuronal AcChoRs were voltagedependent, with an electrical distance of Ϸ0.35. We conclude that strychnine regulates reversibly and noncompetitively the embryonic type of muscle AcChoR and some forms of neuronal AcChoRs. In the former case, strychnine presumably inhibits allosterically the receptor by binding at an external domain whereas, in the latter case, it blocks the open receptorchannel complex.Nicotinic acetylcholine receptors (AcChoRs) are members of a gene superfamily that includes GABA A , glycine, and 5HT 3 receptors (1). They are activated by the neurotransmitter acetylcholine (AcCho), and they mediate fast synaptic transmission at the neuromuscular junction and throughout the vertebrate nervous system (2-4). Additionally, AcChoRs are regulated by a wide variety of substances (5, 6), including strychnine, a selective antagonist of glycine-gated Cl Ϫ channels (7) that inhibits AcChoRs at the neuromuscular junction (8) and different types of neurons (9-13). Moreover, it appears that this inhibition depends on the subtype of nicotinic receptor involved. For instance, in bovine adrenal chromaffin cells and rat hippocampal neurons, strychnine inhibits AcChoRs competitively whereas for ␣ 4 ␤ 2 -containing AcChoRs the inhibition is noncompetitive (10, 13). Here, we report the effects of strychnine on muscle AcChoRs made up of ␣ 1 ␤ 1 ␥␦, ␣ 1 ␤ 1 ␥, or ␣ 1 ␤ 1 ␦ muscle subunits and on two subtypes of neuronal AcChoRs (␣ 2 ␤ 2 or ␣ 2 ␤ 4 ). MATERIALS AND METHODSThe methods were as previously described (14-16). In brief, cDNA clones encoding embryonic mouse muscle AcChoR subunits (␣ 1 , ␤ 1 , ␥, and ␦) or rat neuronal AcChoR subunits (␣ 2 , ␤ 2 , or ␤ 4 ) were used to make cRNAs that were suspended in RNase-free water at a concentration of 1 g͞l. Mixtures then were made with equal quantities of the requ...

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“…The affinity sequence for strychnine action on AcChoRs was (10,13,20); a similar inhibition of the nicotine response by strychnine was found in chicken ciliary ganglion neurons (11).…”

Section: Discussionsupporting

confidence: 58%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Modulation of nicotinic acetylcholine receptors by strychnine

Garcı́a-Colunga

Miledi²

1999

Proc. Natl. Acad. Sci. U.S.A.

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“…The potencies of bicuculline and strychnine in clasp, sling, and LEC fibers (Table 1) were much lower than their reported potencies at GABA A (Maggi et al, 1984;Huang and Johnston, 1990) and glycine receptors (Lynch, 2004), respectively, and within their reported potency for antagonism of nicotinic receptors (Zhang and Feltz, 1991;Kuijpers et al, 1994;Albuquerque et al, 1998;Demuro et al, 2001). Therefore, other antagonists with no reported activity at nicotinic receptors were used: the GABA A antagonist SR95531 (Tonini et al, 1989;Zhang and Feltz, 1991) and the glycine receptor antagonist ginkgolide B (Kondratskaya et al, 2002(Kondratskaya et al, , 2004 in six to eight separate clasp and sling muscle strips from two different donors.…”

Section: Resultsmentioning

confidence: 78%

Pharmacologic Specificity of Nicotinic Receptor-Mediated Relaxation of Muscarinic Receptor Precontracted Human Gastric Clasp and Sling Muscle Fibers within the Gastroesophageal Junction

Braverman

Vegesna²,

Miller³

et al. 2011

J Pharmacol Exp Ther

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Relaxation of gastric clasp and sling muscle fibers is involved the transient lower esophageal sphincter relaxations underlying the pathophysiology of gastroesophageal reflux disease (GERD). These fibers do not contribute tone to the high-pressure zone in GERD patients, indicating their role in pathophysiology. This study identifies some mediators of the nicotine-induced relaxation of muscarinic receptor precontracted gastric clasp and sling fibers. Muscle strips from organ donors precontracted with bethanechol were relaxed with nicotine and then rechallenged after washing and adding inhibitors tetrodotoxin (TTX), the nitric-oxide synthase inhibitor L-nitro-arginine methyl ester (L-NAME), the ␤-adrenoceptor antagonist propranolol, the glycine receptor antagonist strychnine or ginkgolide B, and the GABA A receptor antagonist bicuculline or 2-(3-carboxypropyl)-3-amino-6-(4 methoxyphenyl)pyridazinium bromide [(gabazine) SR95531]. TTX only inhibited clasp fiber relaxations. L-NAME and propranolol inhibited, and ginkgolide B was ineffective in both. SR95531 was ineffective in clasp fibers and partially effective in sling fibers. Strychnine and bicuculline prevented relaxations with low potency, indicating actions not on glycine or GABA A receptors but more consistent with nicotinic receptor blockade. Bethanechol-precontracted fibers were relaxed by the nitric oxide donor S-nitroso-N-acetyl-DL-penicillamine and by the ␤-adrenergic agonist isoproterenol (clasp fibers only) but not by the glycine receptor agonist taurine or glycine or the GABA A agonist muscimol. These data indicate that nicotinic receptor activation mediates relaxation via release of nitric oxide in clasp and sling fibers, norepinephrine acting on ␤-adrenoceptors in clasp fibers, and GABA acting on GABA A receptors in sling fibers. Agents that selectively prevent these relaxations may be useful in the treatment of GERD.

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“…All animal protocols were performed according [27]. Catecholamine secretion experiments were realized according to previous described method [6].…”

Section: Animals and Treatmentmentioning

confidence: 99%

Early glycine supplementation re-establishes adrenal catecholamine secretion in hypothalamic obesity model in rats but does not affect visceral adiposity.

Andreazzi

Silva

Chaves

et al. 2015

JGM

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Obesity is a worldwide epidemic that features a multifactorial syndrome characterized by a chronic positive energetic unbalance. Neonatal administration of monosodium L-glutamate (MSG) causes lesion on the arcuate nucleus of hypothalamus that led to development of obesity in the adult life in rodents characterized by a notorious accumulation of catecholamine in the adrenal medulla. The amino acid glycine induces catecholamine secretion of adrenal medulla. Thus, the objective of our work was to evaluate the possible effects of glycine administration in the MSG-obesity model in rats and investigate its impact on adrenal catecholamine medulla homeostasis. Male Wistar rats received MSG solution (4mg/g body weight)subcutaneously in the cervical area for 5 days after delivery, controls received saline solution. Animals were also divided in two groups, in which one received tap water added with glycine (0.1g/Kg) after weaning on 21 st day until 90 days of life. Biometrical variables, visceral fat pads weight, total content and basal secretion of adrenal cathecolamine were evaluated. Glycine increased Lee index of all tested groups and had no effect on visceral adiposity. However, glycine treatment completely reestablished catecholamine total content and basal secretion of MSG-obese group. In conclusion, although glycine treatment apparently completely reestablishes catecholamine secretion homeostasis it is not sufficient to significant directly reduce visceral adiposity in MSG obesity model in rats. DOI : 10.14302/issn.2572-5424.jgm-14-604Corresponding author: Ana Eliza Andreazzi, Laboratory of Physiology, Department of Physiology Federal University of Juiz de Fora, Rua José Lourenço Kelmer, s/n -Campus Universitário , Bairro São Pedro -CEP: 36036-900 -Juiz de Fora -MG/Brazil, E-mail: anaeliza.andreazzi@ufjf.edu.brRunning title: Glycine reestablishes catecholamine secretion in MSG-rats.

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Inhibitory effect of strychnine on acetylcholine receptor activation in bovine adrenal medullary chromaffin cells

Cited by 17 publications

References 45 publications

Modulation of nicotinic acetylcholine receptors by strychnine

Modulation of nicotinic acetylcholine receptors by strychnine

Pharmacologic Specificity of Nicotinic Receptor-Mediated Relaxation of Muscarinic Receptor Precontracted Human Gastric Clasp and Sling Muscle Fibers within the Gastroesophageal Junction

Early glycine supplementation re-establishes adrenal catecholamine secretion in hypothalamic obesity model in rats but does not affect visceral adiposity.

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