Anatoxin-a a potent ligand for nicotinic cholinergic receptors in rat brain

Zhang, Xiao; Stjernlöf, Peter; Adem, Abdu; Nordberg, Agneta

doi:10.1016/0014-2999(87)90702-3

Cited by 42 publications

(17 citation statements)

References 2 publications

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“…7 and 8) indicating that these effects were mediated by the nicotinic receptors in autonomic ganglia. Thus, our results corroborate the in vitro data that anatoxin-A is a potent nicotinic cholinergic agonist (Carmichael et al, 1979~ Swanson et al, 1986Zhang et al .. 1987). Activation of adrenal medulla was also evident by the increased Ievels of plasma epinephrine after anatoxin-A and nicotine administration ( 6).…”

Section: Discussionsupporting

confidence: 90%

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Cardiovascular effects of anatoxin-A in the conscious rat

Sirén

Feuerstein

1990

Toxicology and Applied Pharmacology

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Cardiovascular Effects of Anatoxin-A in the Conscious Rat. SJREN, A.-L., AND FEUERSTEIN, G. (1990). Toxicol. Appl. Pharmacol. 102,91-100. The effects ofanatoxin-A on mean arterial pressure (MAP), heart rate, cardiac index (CI), and blood flow (BF) in hindquarter (HQ), renal (R). and mesenteric (M) vascular beds were studied after intravenous (iv) and intracerebroventricular (icv) administration in the conscious rat. The pharmacological profile of anatoxin-A was further compared to nicotine administered iv and icv. MAP and heart rate were measured from femoral artery, CI by thermodilution method, and blood flow by Doppler velocimetry. Anatoxin-A and nicotine (30, 100 and 300 1-!g/kg iv) produced an increase in MAP with concomitant bradycardia. The highest doses increased Cl. MBF and RBF decreased due to a vasoconstriction in M and R vasculature. These effects were attenuated by the ganglion blocker chlorisondamine (5 mg/kg, iv). Anatoxin-A ( 100 1-!g/k~ iv) increased plasma epinephrine Ievels by 2-fold with virtually no effect on norepinephrine whereas nicotine ( 100 ~oLg/kg, iv) increased plasma epinephrine and norepinephrine by 20-to 30-fold. Central administration of anatoxin-A and nicotine (30-100 ,ug/kg icv) increased MAP with no effect on heart rate and produced M and R vasoconstriction. In summary, the present study demonstrates that anatoxin-A acts as a nicotinic cholinergic agonist in the c.onscious rat after both systemic and centrat administration. Anatoxin-A and nicotine produced pressor and reno-splanchnic vasoconstrictor responses and at high doses increased cardiac output. These effects were mediated by activation ofthe nicotinic receptors in the adrenal medulla and sympathetic ganglia. However, marked differences were found in the potency ofanatoxin-A versus nicotine to stimulate the sympathoadrenomedullary axis. ti;l 1990 Academic Press,lnc.

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Section: Discussionsupporting

confidence: 90%

“…lt has also been shown to act upon ganglionic muscarinic and nicotinic receptors of the guinea pig ileum (Carmichael et al .. 1979) and to bind. to nicotinic cholinergic receptors in the rat brain homogenates (Zhang et al, 1987).…”

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confidence: 99%

Cardiovascular effects of anatoxin-A in the conscious rat

Sirén

Feuerstein

1990

Toxicology and Applied Pharmacology

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“…Previous in vitro studies have shown that the ( + ), (-), and ( ±) isomers of AnTx-a bind to the nicotinic receptors with varying affinities (SWANSON et al, 1986;ZHANG et al, 1987). When the relative potencies (Icso) of AnTx-a isomers and nicotine were compared, ( + )-AnTx-a was more than 20-fold more potent than ( ± )-AnTx-a and twice as potent than nicotine in inhibiting [ 3 H]-acetylcholine specific binding at the receptor site in the rat brain (ZHANG et al, 1987). Also in recent studies from our Iabaratory, ( ± )-AnTx-a was more than 1 0-fold less potent than nicotine (SIREN and FEUERSTEIN, 1990).…”

Section: Discussionmentioning

confidence: 99%

“…enantiomer (-)-AnTx-a in the racenuc mixture is a weak agonist (SWANSON et al, 1986;ZHANG et al, 1987;KoFUJI et al, 1990).…”

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“…In recent studies, the affinities of ( + )-and ( ± )-AnTx-a for the nicotinic receptors were ~hown to be significantly different. ( + )-AnTx-a binds to high affinity sites (Kd = 6 nM) while ( ± )-AnTx-a binds to low affinity sites (Kd = 125 nM) of nicotinic receptor in the rat's cortex (ZHANG et al, 1987;NoRDBERG et al, 1988;KoFUJI et al, 1990). The present studies were undertaken to investigate in vivo the role of enantiomorphism of the AnTx-a molecule.…”

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Cardio-respiratory changes and mortality in the conscious rat induced by (+)- and (±)-anatoxin-a

Adeyemo

Sirén

1992

Toxicon

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Nicotinic modulation of [3H]D-aspartate outflow from cultured cerebellar granule cells

Bianchi

Tomasini

Antonelli

et al. 2000

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The effect of nicotine on basal and electrically evoked (20 Hz for 20 sec) [(3)H]D-aspartate efflux (assumed as an index of transmitter release) was studied in rat cerebellar granule primary cultures. Nicotine (10-100 nM) increased the basal efflux two to three times and concentration-dependently enhanced the electrically evoked efflux up to ten times. Higher drug concentration (1 microM) underwent rapid desensitization. Facilitation of the efflux was similarly reduced by the nicotinic acetylcholine receptor antagonists, alpha-bungarotoxin and mecamylamine, suggesting the involvement of at least two receptor subtypes containing and lacking alpha(7) subunits, respectively. Since the increased efflux induced by nicotine in granule cells kept at rest or depolarized by KCl 15 mM was antagonized by tetrodotoxin, the involvement of sodium channels by receptors located at preterminal sites was suggested. Taken together, these findings emphasize the role of the cholinergic input in granule cell function and in glutamatergic signaling.

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Anatoxin-a a potent ligand for nicotinic cholinergic receptors in rat brain

Cited by 42 publications

References 2 publications

Cardiovascular effects of anatoxin-A in the conscious rat

Cardiovascular effects of anatoxin-A in the conscious rat

Cardio-respiratory changes and mortality in the conscious rat induced by (+)- and (±)-anatoxin-a

Nicotinic modulation of [3H]D-aspartate outflow from cultured cerebellar granule cells

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