Effect of K+-induced depolarization on carbachol-stimulated inositol tetrakisphosphate accumulation in rat cerebrocortical slices.
Carbachol-stimulated accumulation of labeled IP4 or of total Ins 1,3,4,5-P4 in rat brain cortical slices was maximal in buffer containing 10 mM K+. Iso-osmotic elevation of extracellular K+ to 30 mM did not affect total Ins 1,3,4,5-P4 accumulation but did enhance carbachol stimulated Ins 1,4,5-P3 accumulation. Iso-osmotically elevated K+ suppressed carbachol stimulated accumulation of labeled IP4 while enhancing accumulation of labeled inositol mono-, bis- and trisphosphates. High K+ alone increased basal accumulation of labeled inositol mono-, bis- and trisphosphates, and total Ins 1,4,5-P3, while having no significant effect on accumulation of labeled IP4 or total Ins 1,3,4,5-P4. Long-term incubation with hyper-osmotically elevated K+ potentiated carbachol-stimulated Ins 1,3,4,5-P4 accumulation at 5 min. However, hyper-osmotically elevated K+ suppressed accumulation of labeled IP4 due to carbachol. These results indicate that there is no short-term effect of iso-osmotically elevated K+ on carbachol-stimulated total Ins 1,3,4,5-P4 accumulation. Furthermore, elevating K+ above 10 mM either iso-osmotically or hyper-osmotically suppresses carbachol stimulated accumulation of labeled IP4. The results suggest that the altered Na+/K+ ratio influenced the production of inositol tetrakisphosphates and emphasize the important role of cations such as Na+, K+, and Ca2+ in the receptor-mediated inositol response. Moreover, the results underscore the unique ability of carbachol (a cholinergic agonist) to stimulate significant accumulation of inositol tetrakisphosphate.
Myles
M E
ME
The University of Tennessee, Memphis, Department of Biochemistry 38163, USA.
Fain
J N
JN
D000818:Animals; D002021:Buffers; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000187:drug effects* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007295:Inositol Phosphates / Q000378:metabolism*; D008297:Male; D009994:Osmolar Concentration; D011188:Potassium / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley
D002021:Buffers; D007295:Inositol Phosphates; C081655:inositol-1,3,4,5-tetrakisphosphate; D002217:Carbachol; D011188:Potassium