Metabotropic and ionotropic glutamate receptors mediate opposite effects on periaqueductal gray matter.
Microinjections, into the dorso-lateral periaqueductal gray matter, of N-methyl-D-aspartic acid (NMDA, 0.07-7 nmol/rat) significantly (P < 0.01) increased arterial blood pressure in a dose-related manner. Pretreatment, 5 min before NMDA (7 nmol/rat), in the same area with 2-amino-5-phosphonovaleric acid (2-APV, 5 nmol/rat), a selective antagonist of NMDA receptors, significantly (P < 0.01) reduced NMDA-induced arterial hypertension. trans-(+/-)-1-Amino-1,3-cyclopentanedicarboxylic acid (t-ACPD, 6-30 nmol/rat), an agonist of metabotropic glutamate receptors (mGlu receptors), significantly (P < 0.01) decreased arterial blood pressure when microinjected into the dorsal-lateral periaqueductal gray matter. Pretreatment, 5 min before t-ACPD (30 nmol/rat), in the same area with L-2-amino-3-phosphono-propionate (L-AP-3, 30 nmol/rat), a putative antagonist of the mGlu receptors, was not able to prevent t-ACPD-induced hypotension. Microinjections of L-AP-3 (30 nmol/rat) induced a hypotension similar to the one obtained with t-ACPD at the dose of 6 nmol/rat. From these data we can suggest that mGlu receptors act inversely to the NMDA receptors in the dorso-lateral periaqueductal gray area and that L-AP-3 is a partial agonist rather than an antagonist of mGlu receptors within the periaqueductal gray area.
Leyva
J
J
Institute of Pharmacology and Toxicology, Faculty of Medicine and Surgery, 2nd University of Naples, Italy.
Maione
S
S
Pallotta
M
M
Berrino
L
L
Rossi
F
F
D015763:2-Amino-5-phosphonovalerate / Q000008:administration & dosage / Q000494:pharmacology; D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003515:Cycloleucine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D018690:Excitatory Amino Acid Agonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008845:Microinjections; D016202:N-Methylaspartate / Q000494:pharmacology; D009474:Neurons / Q000502:physiology; D010487:Periaqueductal Gray / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017470:Receptors, Glutamate / Q000187:drug effects / Q000502:physiology*; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects / Q000502:physiology*
D018690:Excitatory Amino Acid Agonists; D018691:Excitatory Amino Acid Antagonists; D017470:Receptors, Glutamate; D018094:Receptors, Metabotropic Glutamate; C000211:2-amino-3-phosphonopropionic acid; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D016202:N-Methylaspartate; D015763:2-Amino-5-phosphonovalerate; D000409:Alanine