Accession Number : ADA255245


Title :   Activation of Phosphoinositide Metabolism by Cholinergic Agents.


Descriptive Note : Final rept. 15 Feb 89-15 Feb 92,


Corporate Author : ALABAMA UNIV IN BIRMINGHAM OFFICE OF RESEARCH AND GRANTS ADMINISTRATION


Personal Author(s) : Jope, Richard S


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a255245.pdf


Report Date : 15 Mar 1992


Pagination or Media Count : 148


Abstract : The primary acute, toxic effect of cholinergic agonists in the central nervous system is seizures. One system activated by cholinergic agonists is the hydrolysis of phosphoinositides (PI), a major site of action of lithium which potentiates convulsions associated with cholinergic agonists. Our goal was to determine how PI hydrolysis is affected by seizures and is modulated, especially by excitatory amino acids (EAA) which mediate brain damage. Modulation of PI hydrolysis was due to a specific EAA receptor activated by quisqualate. Two major effects of quisqualate were identified, activation by itself and inhibition of the effects of other neurotransmitters, especially norepinephrine. Several agents affected these responses, notably calcium and sodium. An inhibitory amino acid had effects generally opposite to quisqualate. Seizures caused changes similar to those of EAA; a selective impairment of norepinephrine-induced PI hydrolysis. Seizures also increased PI hydrolysis mediated by cholinergic receptors. Thus, seizures increased the effects of stimulatory systems (cholinergic, EAA) and reduced the effects of the inhibitory norepinephrine system. The activity of protein kinase C was unaltered by seizures but tyrosine kinase activity was increased. Thus, cholinergic agonist- induced seizures cause major alterations of the important second messenger- generating system of PI hydrolysis, mediated in part by EAA which in turn are influenced by a number of factors, most notably calcium.


Descriptors :   *NEUROTRANSMITTERS , *CENTRAL NERVOUS SYSTEM , *CONVULSIVE DISORDERS , CALCIUM , RATS , PROTEINS , SODIUM , METABOLISM , ACIDS , BRAIN DAMAGE , PHOSPHORUS TRANSFERASES , LABORATORY ANIMALS , AMINO ACIDS , LITHIUM , NERVOUS SYSTEM , ANIMALS , NOREPINEPHRINE , HYDROLYSIS


Subject Categories : Anatomy and Physiology
      Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE