Tags

Type your tag names separated by a space and hit enter

L-proline activates glutamate and glycine receptors in cultured rat dorsal horn neurons.
Mol Pharmacol. 1992 Apr; 41(4):793-801.MP

Abstract

The pharmacological actions of L-proline on excitatory and inhibitory amino acid receptors have been characterized under voltage-clamp conditions, using cultured dissociated neurons from the dorsal horn of the rat spinal cord. At a holding potential of -62 mV, millimolar concentrations of L-proline elicited an inward current that was partially antagonized by D-(-)-2-amino-5-phosphonopentanoic acid (APV), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and strychnine and was virtually abolished (97% block) by a combination of all three antagonists. Currents evoked by D-proline were abolished by strychnine alone. APV-, CNQX-, and strychnine-sensitive components of L-proline-evoked currents were isolated using various combinations of the three antagonists. These currents were identical to currents elicited by N-methyl-D-aspartate (NMDA), kainate, and glycine, respectively, with respect to antagonist specificity, reversal potential, and ionic permeability. The APV- and strychnine-sensitive currents also showed a time dependence similar to that of the currents elicited by NMDA and glycine. EC50 values could not be calculated, because the response did not saturate within the tested range of L-proline concentrations (0.3-50 mM). Estimates of relative potency were obtained, however, by comparison with responses elicited by selective agonists. The APV-sensitive, CNQX-sensitive, and strychnine-sensitive currents evoked by 10 mM L-proline were comparable in size to currents elicited by 15 microM NMDA, 5 microM kainate, and 30 microM glycine, respectively. L-Proline was found to elicit an increase in intracellular [Ca2+] that was dependent upon Ca2+ entry into the cell. These Ca2+ responses were enhanced by strychnine and partially antagonized by APV, CNQX, or Mg2+. Our results using dorsal horn neurons grown in culture indicate that L-proline is a weak agonist at strychnine-sensitive glycine receptors and at both NMDA and non-NMDA glutamate receptors. These observations should help in interpreting the confusing array of L-proline actions that have been described using more intact nervous system preparations. Furthermore, the ability of L-proline to stimulate Ca2+ entry after activation of excitatory amino acid receptors implicates L-proline as a potential endogenous excitotoxin.

Authors+Show Affiliations

Department of Physiology and Cellular Biophysics, Columbia University, New York, New York 10032.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

1349155

Citation

Henzi, V, et al. "L-proline Activates Glutamate and Glycine Receptors in Cultured Rat Dorsal Horn Neurons." Molecular Pharmacology, vol. 41, no. 4, 1992, pp. 793-801.
Henzi V, Reichling DB, Helm SW, et al. L-proline activates glutamate and glycine receptors in cultured rat dorsal horn neurons. Mol Pharmacol. 1992;41(4):793-801.
Henzi, V., Reichling, D. B., Helm, S. W., & MacDermott, A. B. (1992). L-proline activates glutamate and glycine receptors in cultured rat dorsal horn neurons. Molecular Pharmacology, 41(4), 793-801.
Henzi V, et al. L-proline Activates Glutamate and Glycine Receptors in Cultured Rat Dorsal Horn Neurons. Mol Pharmacol. 1992;41(4):793-801. PubMed PMID: 1349155.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - L-proline activates glutamate and glycine receptors in cultured rat dorsal horn neurons. AU - Henzi,V, AU - Reichling,D B, AU - Helm,S W, AU - MacDermott,A B, PY - 1992/4/1/pubmed PY - 1992/4/1/medline PY - 1992/4/1/entrez SP - 793 EP - 801 JF - Molecular pharmacology JO - Mol Pharmacol VL - 41 IS - 4 N2 - The pharmacological actions of L-proline on excitatory and inhibitory amino acid receptors have been characterized under voltage-clamp conditions, using cultured dissociated neurons from the dorsal horn of the rat spinal cord. At a holding potential of -62 mV, millimolar concentrations of L-proline elicited an inward current that was partially antagonized by D-(-)-2-amino-5-phosphonopentanoic acid (APV), 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX), and strychnine and was virtually abolished (97% block) by a combination of all three antagonists. Currents evoked by D-proline were abolished by strychnine alone. APV-, CNQX-, and strychnine-sensitive components of L-proline-evoked currents were isolated using various combinations of the three antagonists. These currents were identical to currents elicited by N-methyl-D-aspartate (NMDA), kainate, and glycine, respectively, with respect to antagonist specificity, reversal potential, and ionic permeability. The APV- and strychnine-sensitive currents also showed a time dependence similar to that of the currents elicited by NMDA and glycine. EC50 values could not be calculated, because the response did not saturate within the tested range of L-proline concentrations (0.3-50 mM). Estimates of relative potency were obtained, however, by comparison with responses elicited by selective agonists. The APV-sensitive, CNQX-sensitive, and strychnine-sensitive currents evoked by 10 mM L-proline were comparable in size to currents elicited by 15 microM NMDA, 5 microM kainate, and 30 microM glycine, respectively. L-Proline was found to elicit an increase in intracellular [Ca2+] that was dependent upon Ca2+ entry into the cell. These Ca2+ responses were enhanced by strychnine and partially antagonized by APV, CNQX, or Mg2+. Our results using dorsal horn neurons grown in culture indicate that L-proline is a weak agonist at strychnine-sensitive glycine receptors and at both NMDA and non-NMDA glutamate receptors. These observations should help in interpreting the confusing array of L-proline actions that have been described using more intact nervous system preparations. Furthermore, the ability of L-proline to stimulate Ca2+ entry after activation of excitatory amino acid receptors implicates L-proline as a potential endogenous excitotoxin. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/1349155/L_proline_activates_glutamate_and_glycine_receptors_in_cultured_rat_dorsal_horn_neurons_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=1349155 DB - PRIME DP - Unbound Medicine ER -