Accumulations of cyclic AMP and inositol phosphates in guinea pig cerebral cortical synaptoneurosomes: enhancement by agents acting at sodium channels.
Activation of alpha 1-adrenergic receptors by norepinephrine in guinea pig cortical synaptoneurosomes augments accumulations of cyclic AMP elicited by 2-chloroadenosine and concomitantly increases formation of inositol phosphates. Various agents that affect calcium channels or sites of action of calcium have little or no effect on cyclic AMP accumulation elicited either with 2-chloroadenosine, or with a 2-chloroadenosine/norepinephrine combination, nor did they markedly affect formation of inositol phosphates elicited by norepinephrine. However, EGTA reduces both cyclic AMP accumulation and inositol phosphate formation. Agents such as batrachotoxin, scorpion (Leiurus) venom and pumiliotoxin B that are active at voltage-dependent sodium channels enhance accumulations of cyclic AMP and inositol phosphates. These effects are blocked by tetrodotoxin. It is proposed that enhanced influx of sodium ions increases phosphatidylinositol metabolism, resulting in formation of diacylglycerols and inositol phosphates, and that the former, through activation of protein kinase, causes an enhancement of cyclic AMP accumulations in brain tissue.
D015762:2-Chloroadenosine; D000241:Adenosine / Q000031:analogs & derivatives / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001496:Batrachotoxins / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002540:Cerebral Cortex / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D006168:Guinea Pigs; D007212:Indolizines; D007295:Inositol Phosphates / Q000378:metabolism*; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010880:Piperidines; D012604:Scorpion Venoms / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D013403:Sugar Phosphates / Q000378:metabolism*; D013574:Synaptosomes / Q000378:metabolism*; D013779:Tetrodotoxin / Q000494:pharmacology
D000470:Alkaloids; D001496:Batrachotoxins; D007212:Indolizines; D007295:Inositol Phosphates; D007473:Ion Channels; D010880:Piperidines; D012604:Scorpion Venoms; D013403:Sugar Phosphates; D015762:2-Chloroadenosine; D013779:Tetrodotoxin; D004533:Egtazic Acid; C031598:pumiliotoxin B; D012964:Sodium; D000242:Cyclic AMP; D000241:Adenosine; D002118:Calcium; D009638:Norepinephrine