title: Lysophosphatidylcholine potentiates vascular contractile responses in rat aorta via activation of tyrosine kinase.
abstract: We previously reported that while lysophosphatidylcholine (LPC) does not itself produce contraction, it significantly potentiates the contractile responses induced by high-K(+), UK14,304 (a selective alpha(2)-adrenoceptor agonist) and phorbol ester in the endothelium-denuded rat aorta. To further investigate this phenomenon, we examined the effects of genistein and tyrphostin B42 (both tyrosine kinase inhibitors) on the LPC-induced potentiation of the contractile responses to high-K(+) and UK14,304 in the endothelium-denuded rat aorta. Although genistein (3 x 10(-6) M, 10(-5) M) did not affect the high-K(+)-induced contractile response, it selectively inhibited the potentiating effect of LPC on the contraction and it strongly inhibited the LPC-induced augmentation of the associated increases in [Ca(2+)](i). Genistein also attenuated the LPC-induced augmentation effects on both the increase in [Ca(2+)](i) and contractile response induced by the UK14,304. In contrast, daidzein (10(-5) M) did not inhibit the potentiating effect of LPC. Tyrphostin B42 (3 x 10(-5) M) attenuated the potentiating effect of LPC on high K(+)-induced contractions. Western blot analysis showed that LPC increased the tyrosine phosphorylation of a number of proteins, including 42 and 44 kDa proteins and 53 - 64 kDa proteins. These protein phosphorylations were inhibited by genistein. Sodium orthovanadate (10(-4) M), a tyrosine phosphatase inhibitor, also markedly enhanced the high-K(+)-induced contractile responses. This enhancing effect was attenuated by genistein. These results suggest that the LPC-induced augmentation of contractile responses in the rat aorta is due to activation of tyrosine kinase, which in turn regulates Ca(2+) influx.
authors.affiliation: Department of Physiology and Morphology, Institute of Medicinal Chemistry, Hoshi University, Shinagawa-ku, Tokyo 142-8501, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Suenaga
authors.forename: Katsuo
authors.initials: K
authors.lastname: Kamata
mesh_terms: D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects* / Q000201:enzymology* / Q000502:physiology; D000068438:Brimonidine Tartrate; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D008244:Lysophosphatidylcholines / Q000494:pharmacology*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects*; D010766:Phosphorylation / Q000187:drug effects; D011188:Potassium / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014662:Vasoconstrictor Agents / Q000494:pharmacology
chemical_list: D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D008244:Lysophosphatidylcholines; D011810:Quinoxalines; D014662:Vasoconstrictor Agents; D000068438:Brimonidine Tartrate; D019833:Genistein; D011505:Protein-Tyrosine Kinases; D011188:Potassium