Increase by lysophosphatidylcholines of smooth muscle Ca2+ sensitivity in alpha-toxin-permeabilized small mesenteric artery from the rat.
1. Pharmacological characterization of different lysophosphatidylcholines was performed based on their effect on the Ca2+ sensitivity of contraction in alpha-toxin-permeabilized rat mesenteric arteries. Furthermore, the effect of noradrenaline on [3H]-myristate-labelled lysophosphatidylcholine levels was assessed, to investigate whether lysophosphatidylcholines could be second messengers. 2. Palmitoyl or myristoyl L-alpha-lysophosphatidylcholine increased the sensitivity to Ca2+, whereas lysophosphatidylcholines containing other fatty acids had less or no effect. 3. L-alpha-phosphatidylcholine, L-alpha-glycerophosphorylcholine, palmitic acid, myristic acid and choline, potential metabolites of lysophosphatidylcholines, did not affect contractions. 4. Noradrenaline (GTP was required) and GTP gamma S increased the sensitivity to Ca2+, and GDP-beta-S inhibited the effect of noradrenaline. Lysophosphatidylcholines, however, had no requirement for GTP and caused sensitization in the presence of GDP-beta-S. 5. Calphostin C, a relatively specific protein kinase C inhibitor, did not affect contraction induced by Ca2+, but abolished the sensitizing effect of lysophosphatidylcholine. 6. Noradrenaline caused no measurable changes in the levels of [3H]-myristate-labelled phosphatidylcholine and lysophosphatidylcholine at 30 s and 5 min stimulation. 7. These results suggest that lysophosphatidylcholines can increase Ca2+ sensitivity through a G-protein-independent, but a protein kinase C-dependent mechanism. However, the role for lysophosphatidylcholines as messengers causing Ca2+ sensitization during stimulation with noradrenaline remains uncertain because no increase in [3H]-myristate labelled lysophosphatidylcholine could be measured during noradrenaline stimulation.
Jensen
P E
PE
Institute of Pharmacology and Danish Biomembrane Research Center, University of Aarhus, Denmark.
Ohanian
J
J
Stausbøl-Grøn
B
B
Buus
N H
NH
Aalkjaer
C
C
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D066298:In Vitro Techniques; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects*; D009119:Muscle Contraction; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism*; D009281:Naphthalenes / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D010738:Type C Phospholipases / Q000494:pharmacology*
D008244:Lysophosphatidylcholines; D009281:Naphthalenes; D011493:Protein Kinase C; D010738:Type C Phospholipases; C058819:calphostin C; D002118:Calcium; D009638:Norepinephrine