Neurotransmitter-specific profiles of inositol phosphates in rat brain cortex: relation to the mode of receptor activation of phosphoinositide phospholipase C.
Phosphoinositide breakdown, as stimulated by six different neurotransmitter receptor agonists (carbachol, serotonin, norepinephrine, trans-(+/-)-aminocyclopentyl-1,3-dicarboxylic acid, endothelin-1 and histamine), has been studied in rat brain cortical slices. The accumulation was monitored of total 3H-inositol phosphates (InsPs) and [3H]CDP-diacylglycerol (CDP-DAG) in [3H]inositol or [3H]cytidine-prelabeled tissue, respectively, and the profile of the major InsPs was quantified as the index log [(inositol 4-monophosphate + inositol 1,4-bisphosphate)/inositol 1-monophosphate]. The efficacy of the six agonists to stimulate the accumulation of CDP-DAG, relative to that of InsPs, was not constant, which revealed varying degrees of defective recycling of DAG to CDP-DAG. The value of the index for the profile of InsPs was not constant either but was characteristic of each agonist. Both parameters (ratio of efficacies CDP-DAG/InsPs and InsPs profile) were not independent and defined two groups of agonists as follows: group a, carbachol and serotonin, with balanced CDP-DAG and InsPs responses, and Ins1P prevailing against inositol 4-monophosphate + inositol 1,4-bisphosphate and group b, norepinephrine, trans-(+/-)-aminocyclopentyl-1,3-dicarboxylic acid, endothelin-1 and histamine, with weak CDP-DAG responses and high accumulation of inositol 4-monophosphate + inositol 1,4-bisphosphate compared with that of inositol 1-monophosphate. In a membrane preparation from brain cortex, only agonists in group a stimulated phospholipase C in the presence of guanosine 5'-O-(3-thiotriphosphate) and in a receptor antagonist-sensitive fashion, which indicated that brain cortical alpha-1, H1, endothelin and glutamate metabotropic receptors stimulate phospholipase C indirectly.(ABSTRACT TRUNCATED AT 250 WORDS)
Sarri
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Departamento de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Autónoma de Barcelona, Spain.
Picatoste
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Claro
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D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000502:physiology*; D004789:Enzyme Activation; D007295:Inositol Phosphates / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000378:metabolism*; D017466:Receptors, Endothelin / Q000378:metabolism*; D017470:Receptors, Glutamate / Q000378:metabolism*; D011969:Receptors, Histamine H1 / Q000378:metabolism*; D011976:Receptors, Muscarinic / Q000378:metabolism*; D011985:Receptors, Serotonin / Q000378:metabolism*; D015290:Second Messenger Systems; D015398:Signal Transduction; D010738:Type C Phospholipases / Q000378:metabolism*
D007295:Inositol Phosphates; D011942:Receptors, Adrenergic, alpha; D017466:Receptors, Endothelin; D017470:Receptors, Glutamate; D011969:Receptors, Histamine H1; D011976:Receptors, Muscarinic; D011985:Receptors, Serotonin; D002217:Carbachol; D008094:Lithium; D010738:Type C Phospholipases; D002118:Calcium; D009638:Norepinephrine