Raising the ambient potassium ion concentration enhances carbachol stimulated phosphoinositide hydrolysis in rat brain hippocampal and cerebral cortical miniprisms.
The influence of the ambient potassium ion concentration ([K+]) upon agonist stimulated hydrolysis of phosphoinositides (PI) has been studied in isolated miniprisms of rat hippocampus and cerebral cortex. When the external [K+] was raised from 6 to 18 mmol/l, there was little or no increase in the hydrolysis of PI in the absence of agonist, however, carbachol (100 mumol/l) stimulated hydrolysis was greatly enhanced in both brain regions studied. Thus, carbachol stimulated the hydrolysis of PI to 146% and 386% of control levels at potassium concentrations of 5.88 and 18.2 mmol/l, respectively, in the rat hippocampus. A similar enhancement of muscarine (100 mumol/l) stimulation was observed in cortical miniprisms with 18 mmol/l [K+]. A further enhancement was seen at higher ambient [K+], although basal hydrolysis of PI was then also increased. The carbachol-stimulated hydrolysis of PI found at both 6 and raised [K+] was prevented by atropine (1 and 10 mumol/l) and tetraethylammonium (20 mmol/l), but not by 10 mmol/l Mg2+. Pirenzepine (50 nmol/l) also reduced this response. The ions Cs+ and Rb+ (but not Li+ or Tris+) produced a similar enhancement of the carbachol stimulation to that found with K+. At a buffer [K+] of 6 mmol/l, noradrenaline (100 mumol/l) produced a 2-fold increase in the hydrolysis of PI whereas 5-hydroxytryptamine (100 mumol/l) and histamine (500 mumol/l) had little or no effect. However, histamine and 5-hydroxytryptamine did stimulate the hydrolysis of PI when [K+] was increased. Miniprism ATP content was not changed by a rise in [K+] to 18 mmol/l. The significance of these results is discussed in terms of the postsynaptic cellular events following cholinergic stimulation.
D006916:5-Hydroxytryptophan / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006868:Hydrolysis; D066298:In Vitro Techniques; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism*; D051381:Rats
D010716:Phosphatidylinositols; D006632:Histamine; D000255:Adenosine Triphosphate; D002217:Carbachol; D006916:5-Hydroxytryptophan; D011188:Potassium; D009638:Norepinephrine