Glutamatergic regulation of [3H]acetylcholine release in striatal slices of normotensive and spontaneously hypertensive rats.
It has been proposed that central cholinergic neurons may actively participate in blood pressure control and other cardiovascular regulations. The present study was performed to investigate the role of the glutamate receptors in the regulation of acetylcholine release in rat central nervous system in vitro. In the Mg2+-free condition, L-glutamate, an endogenous ligand for glutamate receptors, elicited [3H]acetylcholine release from striatal slices of Sprague-Dawley rats in a dose-related fashion. Glycine, an allosteric agonist for the N-methyl-D-aspartate type of glutamate receptor, significantly potentiated the increase in [3H]acetylcholine release evoked by L-glutamate. A non-competitive N-methyl-D-aspartate receptor antagonist, MK-801, blocked the L-glutamate-induced increase in [3H]acetylcholine release, although MK-801 had no effects on its own. In spontaneously hypertensive rats, the facilitatory effect of L-glutamate on [3H]acetylcholine release was significantly smaller than that in Wistar-Kyoto rats. Moreover, L-glutamate in combination with glycine increased the release of [3H]acetylcholine to a lesser extent in SHR than in WKY rats. These results show that L-glutamate increased acetylcholine release from rat striatum, which was highly dependent on the N-methyl-D-aspartate type of glutamate receptor. Furthermore, the lesser facilitation of acetylcholine release by L-glutamate in spontaneously hypertensive rats suggests that the excitatory amino acid may be, at least in part, involved in the regulation of central cholinergic nerve activity in hypertension.
Tsuda
K
K
Neurochemistry Research Laboratories, New York University Medical Center, New York, USA.
Tsuda
S
S
Goldstein
M
M
Nishio
I
I
Masuyama
Y
Y
D000109:Acetylcholine / Q000378:metabolism*; D000818:Animals; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D018698:Glutamic Acid / Q000502:physiology*; D005998:Glycine / Q000494:pharmacology; D006973:Hypertension / Q000235:genetics / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D017072:Neostriatum / Q000378:metabolism*; D010275:Parasympathetic Nervous System / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
D018691:Excitatory Amino Acid Antagonists; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; D000109:Acetylcholine; D005998:Glycine