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 Ins 1P 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. These results show that both the efficacy of the CDP-DAG response and the profile of InsPs are characteristics inherent to the proper mode of receptor activation of phospholipase C, either direct (via receptor-G protein-phospholipase C interaction) or indirect, probably secondary to calcium entry.
|Journal||Journal of Pharmacology and Experimental Therapeutics|
|Publication status||Published - 1 Jan 1995|
Sarri, E., Picatoste, F., & Claro, E. (1995). Neurotransmitter-specific profiles of inositol phosphates in rat brain cortex: Relation to the mode of receptor activation of phosphoinositide phospholipase C1. Journal of Pharmacology and Experimental Therapeutics, 272(1), 77-84.