CYCLIC NUCLEOTIDES AND OTHER SECOND MESSENGERS IN THE NERVOUS SYSTEM

生理功能在不同的细胞中由a

Physiological functions are mediated in different cells by a variety second messengers including cyclic AMP and cyclic GMP. Ions such as calcium, sodium and magnesium can serve after translocation through ion channels or by transport proteins as second messengers to activate release of ions, and activation of contratile proteins, protein kinases, phospholipases, ATPases and other enzymes. Enzymatic hydrolysis of phospholipids can also generate second messengers such as arachidonate, which serves as a precursor of prostanoids; diacylglycerides, which serve as activators of protein kinase C; and inositol phosphates, which serve as mobilizers of internal calcium ions. Receptors of various types serve to modulate generation of second messengers. The interrelationships of second messengers and receptors and the delineation of selective agents for such systems have been investigated. Phorbol esters, which like the diacylglycerides activate protein kinase C, inhibit receptor-mediated formation of cyclic AMP in a neuroblastoma-hybrid cell line. A variety of receptor agonists and agents that activate voltage-dependent sodium or calcium channels cause activation of phospholipase C and breakdown of phosphoinositides in synaptoneurosomes. Phorbol esters inhibit these responses. A small subpopulation of sodium channels with high sensitivity to cadmium ions and low sensitivity to tetrodotoxin appear losely associated with phosphoinositude metabolism. Adenosine stimulates cyclic AMP formation through an A2 receptor and inhibits cyclic AMP formation through an A1 receptor. A series of adenosine analogs have been delinated for pharmacological characterization of receptors involved in physiological functions of adenosine. A variety of non-xanthine heterocycles, including a series of N6- substituted-9-methyladenines have been characterized as adenosine receptor antagonists certain xanthine analogs have been shown to have selective effects as antagonists of the hypotensive effects of adenosine, the cardiac depressant effects of adenosine and the synergism between adenosine and nicotine.