Marked dissociation between intracellular Ca2+ level and contraction on exposure of rat aorta to lysophosphatidylcholine.
We investigated the relationship between tension development and the cytosolic free Ca2+ level ([Ca2+]i) on exposure of the endothelium-denuded isolated rat aorta to palmitoyl-L-alpha-lysophosphatidylcholine. Lysophosphatidylcholine concentration-dependently induced a gradual increase in [Ca2+]i. Application of 10(-4) M lysophosphatidylcholine induced a large and sustained tonic increase in [Ca2+]i (the peak [Ca2+]i was 125.2 +/- 11.5% of the 80 mM K+-induced response) but only a small contraction (4.0 +/- 1.4% of the 80 mM K+ induced contraction). The sustained increase in [Ca2+]i was attenuated when extracellular Ca2+ was removed but it was unaffected by verapamil or 1-(5-isoquinolinesulphonyl)-2-methylpiperazine dihydrochloride (H-7). Digitonin also produced a gradual increase in [Ca2+]i but with a pronounced contraction. Triton X-100 (0.1%) produced a marked elevation in [Ca2+]i with no detectable contraction. Triton X-100, however, caused a rapid leakage of fura PE-3. Treatment with 10(-4) M lysophosphatidylcholine for 1 or 2 h did not affect the contractile response induced by 80 mM K+ and this treatment did not release lactate dehydrogenase from the rat aorta. Treatment with lysophosphatidylcholine did not affect either the cyclic AMP level or the cyclic GMP level in endothelium-denuded aortic tissues. These results show that in the rat aorta lysophosphatidylcholine produces a large increase in [Ca2+]i (possibly in a non-contractile compartment) which does not induce contraction. Thus, the increase in [Ca2+]i induced by lysophosphatidylcholine (i) requires external Ca2+ but is not due to an increased Ca2+ influx through voltage-dependent L-type Ca2+ channels, (ii) is not primarily due to protein kinase C activation and (iii) is probably not due to a detergent action (like those of digitonin and triton X-100). The relative lack of a contractile response to lysophosphatidylcholine is not due to formation of cyclic AMP or cyclic GMP.
Suenaga
H
H
Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Tokyo, Japan.
Kamata
K
K
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000502:physiology; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D008244:Lysophosphatidylcholines; D009569:Nitric Oxide; D000242:Cyclic AMP; D011493:Protein Kinase C; D006152:Cyclic GMP; D002118:Calcium