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Noradrenaline Antagonizes and Ouabain Potentiates the Effects of iV‐Methyl‐D‐Aspartate on Rat Cerebellar Cyclic GMP Production
Author(s) -
Carter C. J.,
Gueug J.,
Scatton B.
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb01831.x
Subject(s) - methoxamine , oxymetazoline , chemistry , endocrinology , phentolamine , medicine , idazoxan , nmda receptor , phenylephrine , agonist , ouabain , antagonist , pharmacology , propranolol , prazosin , biology , biochemistry , receptor , organic chemistry , blood pressure , sodium
Noradrenaline potently antagonizes the effects of N ‐methyl‐D‐aspartate (NMDA) (80 μ M ) on cyclic GMP production in immature rat cerebellar slices in vitro (IC50 = 0.6 μ M ). The effect is stereospecific (D‐noradrenaline, IC50 = 100 μ M ), and also observed with adrenaline (IC 50 = 0.5 μ M ) and isoprenaline (IC 50 = 1.2 μ M ). The α 1 ‐adrenoceptor agonists methoxamine or phenylephrine or the mixed α/α 2 agonists oxymetazoline or xylometazoline (100 μ M ) do not block the effects of NMDA, but the α 2 ‐adrenoceptor agonist clonidine is weakly active (IC50 = 200 μ M ). Salbutamol and terbutaline were also inactive except at high concentrations (300 μ M ), as were a number of other catechol and phenylethylamine derivatives. The antagonistic effects of noradrenaline on the NMDA response were insensitive to phentolamine, atenolol, or propranolol (up to 100 μ M ), but were blocked by the α 2 antagonist idazoxan (1–10 μ M ). The Na + ,K + ‐ATPase inhibitor ouabain (0.1–10 μ M ) markedly potentiates the effects of NMDA in this model, and also antagonizes and reverses the ability of noradrealine (10 μ M ) to block the effects of NMDA. The results suggest that noradrenaline and Na + ,K + ‐ATPase activity have potent modulatory effects on the NMDA response.