Phospholemman does not participate in forskolin-induced swine carotid artery relaxation.
Phosphorylation of phospholemman (PLM) on ser68 has been proposed to at least partially mediate cyclic AMP (cAMP) mediated relaxation of arterial smooth muscle. We evaluated the time course of the phosphorylation of phospholemman (PLM) on ser68, myosin regulatory light chains (MRLC) on ser19, and heat shock protein 20 (HSP20) on ser16 during a transient forskolin-induced relaxation of histamine-stimulated swine carotid artery. We also evaluated the dose response for forskolin- and nitroglycerin-induced relaxation in phenylephrine-stimulated PLM-/- and PLM+/+ mice. The time course for changes in ser19 MRLC dephosphorylation and ser16 HSP20 phosphorylation was appropriate to explain the forskolin-induced relaxation and the recontraction observed upon washout of forskolin. However, the time course for changes in ser68 PLM phosphorylation was too slow to explain forskolin-induced changes in force. There was no difference in the phenylephrine contractile dose response or in forskolin-induced relaxation dose response observed in PLM-/- and PLM+/+ aortae. In aortae precontracted with phenylephrine, nitroglycerin induced a slightly, but significantly greater relaxation in PLM-/- compared to PLM+/+ aortae. These data are consistent with the hypothesis that ser19 MRLC dephosphorylation and ser16 HSP20 phosphorylation are involved in forskolin-induced relaxation. Our data suggest that PLM phosphorylation is not significantly involved in forskolin-induced arterial relaxation.
Meeks
M K
MK
Cardiovascular Division, Department of Internal Medicine, University of Virginia Health System, Charlottesville, Virginia, USA.
Han
S
S
Tucker
A L
AL
Rembold
C M
CM
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism; D002339:Carotid Arteries / Q000187:drug effects* / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D050886:HSP20 Heat-Shock Proteins / Q000378:metabolism; D008565:Membrane Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D018994:Myosin Light Chains / Q000378:metabolism; D005996:Nitroglycerin / Q000494:pharmacology; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D013552:Swine; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000494:pharmacology*
D050886:HSP20 Heat-Shock Proteins; D008565:Membrane Proteins; D018994:Myosin Light Chains; D010750:Phosphoproteins; D014665:Vasodilator Agents; C069141:phospholemman; D005576:Colforsin; D000242:Cyclic AMP; D005996:Nitroglycerin