Tachycardia after glutamate injection in rat spinal cord is not blocked by kynurenate or mimicked by metabotropic agonists.
1. We have used microinjections of glutamate, an ionotropic excitatory amino acid receptor antagonist (kynurenate) and selective ionotropic (NMDA and kainate) and metabotropic (1S-3R-ACPD, trans-ACPD and L-AP4) receptor agonists in the thoracic IML of the rat to define the receptors mediating the tachycardia produced by excitatory amino acid antagonists. 2. Injection of glutamate (delta heart rate = 76 +/- 8 beats/min n = 16), NMDA (delta heart rate = 116.5 +/- 5 beats/min n = 6) or kainate (delta heart rate = 92 +/- 22 beats/min n =6 evokes a tachycardia when injected into the thoracic intermediolateral column. Kynurenate blocked the response to NMDA (-2% of initial response) and markedly attenuated the response to kainate (14% of initial response) but did not alter the response to glutamate (106% of initial response). 3. IS-3R-ACPD did not elicit a tachycardia when injected into the thoracic intermediolateral column and neither trans-ACPD nor L-AP4 induced a tachycardia after kynurenate injection into the thoracic intermediolateral column. 4. Thus stimulation of either NMDA or AMPA/kainate receptors elicits tachycardia in rat thoracic spinal cord but glutamate also activates another receptor type to elicit a tachycardia. The lack of a tachycardia when trans-ACPD, 1S-3R-ACPD or L-AP4 were injected into the thoracic spinal cord suggests that the kynurenate resistant tachycardia elicited by glutamate is not mediated by metabotropic receptors. The kynurenate resistant tachycardia elicited by glutamate is not mediated by any of the known excitatory amino acid receptor types.
Arnolda
L F
LF
Department of Medicine, Flinders Medical Centre, Adelaide, Australia.
Pilowsky
P M
PM
Minson
J B
JB
Llewellyn-Smith
I J
IJ
Chalmers
J P
JP
D000613:Aminobutyrates / Q000494:pharmacology; D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology*; D018698:Glutamic Acid / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007278:Injections, Spinal; D007608:Kainic Acid / Q000494:pharmacology; D007736:Kynurenic Acid / Q000494:pharmacology*; D016202:N-Methylaspartate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D051381:Rats; D011921:Rats, Inbred WKY; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists; D013116:Spinal Cord / Q000187:drug effects*; D013610:Tachycardia / Q000139:chemically induced* / Q000517:prevention & control
D000613:Aminobutyrates; D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D018094:Receptors, Metabotropic Glutamate; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D018698:Glutamic Acid; D016202:N-Methylaspartate; D007736:Kynurenic Acid; C012729:2-amino-4-phosphonobutyric acid; D007608:Kainic Acid