Enhancement by potassium of carbachol-stimulated inositol phospholipid breakdown in rat cerebral cortical miniprisms: comparison with other depolarising agents.
Increasing the [K+] in the assay medium from 5.7 to 17.8 mM produces a large enhancement of the inositol phospholipid breakdown response to the muscarinic agonist carbachol in rat cerebral cortical miniprisms, with minor effects on basal inositol phospholipid breakdown. This effect is also found with Rb+. The enhancement by a raised [K+] is not accompanied by a change in the composition of the labelled polyphosphoinositides. The carbachol-stimulated inositol phospholipid breakdown at 17.8 and 42.7 mM K+ was antagonised by veratrine (5-80 microM), 4-aminopyridine (5 mM), and tetraethylammonium (20 mM). These compounds, however, also inhibited the binding of [3H]quinuclidinyl benzilate to cortical membranes. BRL 34915 (0.2-20 microM) was without significant effect on carbachol-stimulated inositol phospholipid breakdown at either 5.7 or 17.8 mM K+.Mg2+ (10 mM) considerably reduced the carbachol-stimulated inositol phospholipid breakdown at 17.8, but not 42.7, mM K+. Inositol phospholipid breakdown was also stimulated, albeit to a small extent, by L-glutamate (100-3,000 microM) and quisqualate (1-100 microM), with the stimulation being additive to that produced by carbachol at both 5.7 and 17.8 mM K+. N-Methyl-D-aspartate (10-1,000 microM in Mg2+-free medium) had no significant effect on basal inositol phospholipid breakdown and had little or no effect on carbachol-stimulated inositol phospholipid breakdown at either 5.7 or 17.8 mM K+. It is concluded that it may not be correct to ascribe wholly the enhancement by K+ of carbachol-stimulated inositol phospholipid breakdown to the tissue-depolarising actions of this ion and that other actions of K+ may be involved.
Tiger
G
G
Department of Pharmacology, University of Umeå, Sweden.
Björklund
P E
PE
Cowburn
R F
RF
Fowler
C J
CJ
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D002217:Carbachol / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism*; D006652:Histological Techniques; D066298:In Vitro Techniques; D007473:Ion Channels / Q000502:physiology; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D014702:Veratrine / Q000494:pharmacology
D000596:Amino Acids; D007473:Ion Channels; D010716:Phosphatidylinositols; D002217:Carbachol; D014702:Veratrine; D008274:Magnesium; D011188:Potassium