Pharmacological characterization of phosphoinositide-linked glutamate receptor excitation of hippocampal neurons.
Pharmacological studies of glutamate receptor stimulation of the phosphoinositide (PI) system have demonstrated that this response is blocked by several agents: 2-amino-3-phosphonopropionate (AP3), phorbol esters and in some preparations pertussis toxin. In electrophysiological studies of CA1 pyramidal neurons, we have found that pertussis toxin and AP3 (1-2 mM) do not block either the membrane depolarization or inhibition of the slow afterhyperpolarization elicited by trans-1-aminocyclopentyl-1,3-dicarboxylate (ACPD; 30 microM), a selective agonist of the PI-linked glutamate receptor. However, phorbol 12,13-diacetate (1-1.5 microM) which itself blocks the slow afterhyperpolarization, completely blocks the membrane depolarizing response elicited by ACPD. These results add to growing evidence for heterogeneity among PI-linked glutamate receptor responses.
Stratton
K R
KR
Department of Neuroscience, John Hopkins University School of Medicine, Baltimore, MD 21205.
Worley
P F
PF
Baraban
J M
JM
D000409:Alanine / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D003515:Cycloleucine / Q000031:analogs & derivatives / Q000494:pharmacology; D004594:Electrophysiology; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D066298:In Vitro Techniques; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D037342:Pertussis Toxin; D010703:Phorbol Esters / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism* / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010703:Phorbol Esters; D010716:Phosphatidylinositols; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; D013757:Tetraethylammonium Compounds; D010566:Virulence Factors, Bordetella; C000211:2-amino-3-phosphonopropionic acid; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D037342:Pertussis Toxin; D000409:Alanine