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Subunit-specific potentiation of recombinant N-methyl-D-aspartate receptors by histamine.
Mol Pharmacol. 1994 Sep; 46(3):531-41.MP

Abstract

Histamine has numerous functions in the brain and has recently been shown to modulate responses of N-methyl-D-aspartate (NMDA) receptors on hippocampal neurons by a mechanism that does not involve classical histamine receptors. In the present work, voltage-clamp recording was used to study the effects of histamine on recombinant NMDA receptors expressed in Xenopus oocytes, to determine whether histamine acts directly on NMDA receptors and to investigate the subunit specificity of the effects of histamine. Histamine potentiated responses to NMDA at heteromeric NR1/NR2 receptors containing splice variants of the NR1 subunit (NR1A or NR1E) that lack the amino-terminal insert, together with the NR2B subunit but not the NR2A or NR2C subunit. Stimulation by histamine (EC50 = 10 microM) had a novel profile, involving a rapid increase in the magnitude of NMDA-induced currents followed by slow (approximately 1-min) desensitization to a steady state level. Desensitization of the response to histamine was time dependent and could occur in the absence of receptor activation by NMDA. Stimulation by histamine was dependent on the concentration of agonist used to activate NR1A/NR2B receptors and was seen with high but not low concentrations of NMDA and glutamate. The effect of histamine was not blocked by classical histamine receptor antagonists but was mimicked by the histamine metabolite 1-methylhistamine. At a high concentration (1 microM) histamine produced a voltage-dependent inhibition of NMDA currents at NR1A/NR2B receptors and at receptors (NR1B/NR2B) that are not sensitive to stimulation by histamine. The results suggest that histamine acts directly at a novel recognition site on some subtypes of NMDA receptors to increase their activity.

Authors+Show Affiliations

Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia 19104-6084.

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

7935335

Citation

Williams, K. "Subunit-specific Potentiation of Recombinant N-methyl-D-aspartate Receptors By Histamine." Molecular Pharmacology, vol. 46, no. 3, 1994, pp. 531-41.
Williams K. Subunit-specific potentiation of recombinant N-methyl-D-aspartate receptors by histamine. Mol Pharmacol. 1994;46(3):531-41.
Williams, K. (1994). Subunit-specific potentiation of recombinant N-methyl-D-aspartate receptors by histamine. Molecular Pharmacology, 46(3), 531-41.
Williams K. Subunit-specific Potentiation of Recombinant N-methyl-D-aspartate Receptors By Histamine. Mol Pharmacol. 1994;46(3):531-41. PubMed PMID: 7935335.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Subunit-specific potentiation of recombinant N-methyl-D-aspartate receptors by histamine. A1 - Williams,K, PY - 1994/9/1/pubmed PY - 1994/9/1/medline PY - 1994/9/1/entrez SP - 531 EP - 41 JF - Molecular pharmacology JO - Mol Pharmacol VL - 46 IS - 3 N2 - Histamine has numerous functions in the brain and has recently been shown to modulate responses of N-methyl-D-aspartate (NMDA) receptors on hippocampal neurons by a mechanism that does not involve classical histamine receptors. In the present work, voltage-clamp recording was used to study the effects of histamine on recombinant NMDA receptors expressed in Xenopus oocytes, to determine whether histamine acts directly on NMDA receptors and to investigate the subunit specificity of the effects of histamine. Histamine potentiated responses to NMDA at heteromeric NR1/NR2 receptors containing splice variants of the NR1 subunit (NR1A or NR1E) that lack the amino-terminal insert, together with the NR2B subunit but not the NR2A or NR2C subunit. Stimulation by histamine (EC50 = 10 microM) had a novel profile, involving a rapid increase in the magnitude of NMDA-induced currents followed by slow (approximately 1-min) desensitization to a steady state level. Desensitization of the response to histamine was time dependent and could occur in the absence of receptor activation by NMDA. Stimulation by histamine was dependent on the concentration of agonist used to activate NR1A/NR2B receptors and was seen with high but not low concentrations of NMDA and glutamate. The effect of histamine was not blocked by classical histamine receptor antagonists but was mimicked by the histamine metabolite 1-methylhistamine. At a high concentration (1 microM) histamine produced a voltage-dependent inhibition of NMDA currents at NR1A/NR2B receptors and at receptors (NR1B/NR2B) that are not sensitive to stimulation by histamine. The results suggest that histamine acts directly at a novel recognition site on some subtypes of NMDA receptors to increase their activity. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/7935335/Subunit_specific_potentiation_of_recombinant_N_methyl_D_aspartate_receptors_by_histamine_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=7935335 DB - PRIME DP - Unbound Medicine ER -