Excitatory amino acid-induced phosphoinositide turnover in guinea pig cerebral cortical slices: selective enhancement by spermine of the response to DL-1-aminocyclopentane-trans-1,3-dicarboxylate.
In the presence of 1 mM spermine, accumulations of 3H labelled inositol phosphates elicited by quisqualate (100 microM) and 1-aminocyclopentane-trans-1,3-dicarboxylate (t-ACPD, 300 microM) were significantly enhanced by 21 and 26%, respectively, without a significant alteration in the accumulation elicited by L-glutamate (10 mM) or DL-alpha-amino-3-hydroxy-5-methyl-4-isoxalone propionate (10 microM). Analysis of concentration-response data indicated that the presence of spermine led to an increase in the maximal response to t-ACPD without altering the EC50 value. The stimulatory effect of spermine on the accumulation of t-ACPD-elicited 3H-inositol phosphates was not reversed by ifenprodil or diethylenetriamine (putative polyamine site antagonists), by agents that activate or inhibit protein kinase C, or by calcium channel blockade, but was abolished in the presence of elevated extracellular calcium ion concentration. We conclude that spermine enhances the phosphoinositide turnover in guinea pig cerebral cortical slices elicited by the "metabotropic" excitatory amino acid receptor. The site through which the action of spermine is mediated remains to be defined, but it is apparently distinct from that suggested to modulate N-methyl-D-aspartate receptor activity.
Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre, England, U.K.
S P
SP
Alexander
D A
DA
Kendall
S J
SJ
Hill
D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D003515:Cycloleucine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D005971:Glutamates / Q000494:pharmacology; D006168:Guinea Pigs; D006868:Hydrolysis / Q000187:drug effects; D008297:Male; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D010880:Piperidines / Q000494:pharmacology; D011073:Polyamines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000494:pharmacology; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface / Q000187:drug effects / Q000502:physiology; D013096:Spermine / Q000494:pharmacology*; D019311:Staurosporine
D000317:Adrenergic alpha-Antagonists; D000470:Alkaloids; D000596:Amino Acids; D005971:Glutamates; D010716:Phosphatidylinositols; D010880:Piperidines; D011073:Polyamines; D017459:Receptors, Amino Acid; D011956:Receptors, Cell Surface; C005391:diethylenetriamine; D003515:Cycloleucine; C036361:1-amino-1,3-dicarboxycyclopentane; D013096:Spermine; D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C; D019311:Staurosporine; C010739:ifenprodil; D002118:Calcium