Characterization of cholinergic muscarinic receptor-stimulated phosphoinositide metabolism in brain from immature rats

Journal Article · Tue May 01 04:00:00 EDT 1990 · Journal of Pharmacology and Experimental Therapeutics; (USA)

OSTI ID:6746803

Balduini, W; Murphy, S D; Costa, L G ^[1]

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1. Univ. of Washington, Seattle (USA)

Hydrolysis of phosphoinositides elicited by stimulation of cholinergic muscarinic receptors has been studied in brain from neonatal (7-day-old) rats in order to determine: (1) whether the neonatal rat could provide a good model system to study this signal-transduction pathway; and (2) whether potential differences with adult nerve tissue would explain the differential, age-related effects of cholinergic agonists. Accumulation of (3H) inositol phosphates in (3H)inositol prelabeled slices from neonatal and adult rats was measured as an index of phosphoinositide metabolism. Full (acetylcholine, methacholine, carbachol) and partial (oxotremorine, bethanechol) agonists had qualitatively similar, albeit quantitatively different, effects in neonatal and adult rats. Atropine and pirenzepine effectively blocked the carbachol-induced response with inhibition constants of 1.2 and 20.7 nM, respectively. In all brain areas, response to all agonists was higher in neonatal than adult rats, and in hippocampus and cerebral cortex the response was higher than in cerebellum or brainstem. The relative intrinsic activity of partial agonists was higher in the latter two areas (0.6-0.7) than in the former two (0.3-0.4). Carbachol-stimulated phosphoinositide metabolism in brain areas correlated well with the binding of (3H)QNB (r2 = 0.627) and, particularly, with (3H)pirenzepine (r2 = 0.911). In cerebral cortex the effect of carbachol was additive to that of norepinephrine and glutamate. The presence of calcium (250-500 microM) was necessary for maximal response to carbachol to be elicited; the EC50 value for Ca2+ was 65.4 microM. Addition of EDTA completely abolished the response. Removal of sodium ions from the incubation medium reduced the response to carbachol by 50%.

• OSTI ID: 6746803
• Journal Information: Journal of Pharmacology and Experimental Therapeutics; (USA), Journal Name: Journal of Pharmacology and Experimental Therapeutics; (USA) Vol. 253:2; ISSN 0022-3565; ISSN JPETA
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ADULTS
AGE DEPENDENCE
AGE GROUPS
AMINO ACIDS
ANIMALS
AUTONOMIC NERVOUS SYSTEM AGENTS
BIOLOGICAL PATHWAYS
BODY
BRAIN
CARBOXYLIC ACIDS
CENTRAL NERVOUS SYSTEM
CHELATING AGENTS
DRUGS
EDTA
ESTERS
HYDROGEN COMPOUNDS
ISOTOPE APPLICATIONS
LIPIDS
MAMMALS
MEMBRANE PROTEINS
METABOLISM
NEONATES
NERVES
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
ORGANS
PARASYMPATHOLYTICS
PARASYMPATHOMIMETICS
PHOSPHOLIPIDS
PROTEINS
RATS
RECEPTORS
RODENTS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
VERTEBRATES