Abstract
The properties of muscarinic agonist stimulated phosphoinositide turnover in canine atrial slices were investigated. In slices prelabeled with 32P i , carbachol stimulated a 20–30% decrease of 32P-labeled phosphatidylinositol 4'-phosphate (PIP) and phosphatidylinositol 4',5'-bisphosphate (PIP 2) content within 10–15 sec. This was followed by a resynthesis of these lipids to control levels after 30 sec. Carbachol-stimulated PIP and PIP 2 turnover was followed by a relatively slower increase in 32P incorporation into phosphatidylinositol (PI) and phosphatidic acid (PA) which was maximal after 5–10 min. Carbachol increased 32P-labeling of PA and PI in most regions of right and left atria with equal effectiveness. Muscarinic receptor stimulated increases in PA and PI labeling showed high specificity for certain muscarinic agonists and, unlike most tissues, this muscarinic receptor mediated phospholipid effect was dependent on extracellular calcium. Carbachol did not increase 32P incorporation into PA and PI if Mn 2+, Co 2+, Mg 2+, or La 3+ was substituted for extracellular Ca 2+. Unlike other muscarinic agonists, acetylcholine increased 32P incorporation into phosphatidylcholine in addition to PA and PI. Low concentrations of calcium channel blockers, verapamil, nifedipine or diltiazem, did not block carbachol-stimulated changes in PA and PI labeling in the presence of Ca 2+; however, higher concentrations (⩾10 μM) of verapamil increased PA and PI labeling. Ouabain enhanced carabachol-stimulated 32P incorporation into PA but attenuated incorporation into PI. The mechanisms associated with the actions of these agents on phospholipid metabolism and their possible physiological significance are discussed.
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Disclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.