Phospholipid methylation in canine cardiac membranes. Relations to beta-adrenergic receptors and digitalis receptors.
Phospholipid methylation of canine cardiac membranes was studied in vitro to determine its relationship to the regulation and function of beta-adrenergic and digitalis receptors. Cardiac membranes were prepared from the left ventricle of mongrel dogs. Phospholipid methylation was assayed by measuring [3H] methyl incorporation after incubation with methyl donor S-adenosyl-L-[methyl-3H] methione at 37 degrees C. The reaction of phospholipid methylation had an optimum pH around 9 and a linear time course of up to 60 min. The reaction was inhibited by the addition of S-adenosyl-L-homocysteine, a known antagonist of biological transmethylation. L-isoproterenol enhanced phospholipid methylation markedly, but ouabain had no effect. On the other hand, after phospholipid methylation in cardiac membranes was stimulated by pre-incubation with S-adenosyl-L-methionine for 60 min at 37 degrees C, [125I] iodohydroxybenzylpindolol binding to the membranes was increased. The number of the beta-adrenergic receptor binding sites (Bmax), calculated from Scatchard analysis in cardiac membranes of 3 dogs significantly increased. On the other hand, [3H] ouabain binding and Na+, K+, Mg2+-ATPase activity were not increased. The increase in [125I] iodohydroxybenzylpindolol binding was inhibited by the addition of S-adenosyl-L-homocysteine. These binding suggest that phospholipid methylation is closely related to beta-adrenergic receptors, but not digitalis receptors in cardiac membranes.
D000818:Animals; D004285:Dogs; D006863:Hydrogen-Ion Concentration; D008566:Membranes / Q000378:metabolism; D008745:Methylation; D009206:Myocardium / Q000378:metabolism*; D010743:Phospholipids / Q000378:metabolism*; D010869:Pindolol / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000378:metabolism; D011941:Receptors, Adrenergic / Q000502:physiology*; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D011955:Receptors, Drug / Q000502:physiology*; D012436:S-Adenosylmethionine / Q000494:pharmacology; D000254:Sodium-Potassium-Exchanging ATPase
D010743:Phospholipids; D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D011955:Receptors, Drug; C027082:digitalis receptor; C011878:iodohydroxybenzylpindolol; D012436:S-Adenosylmethionine; D010869:Pindolol; D000254:Sodium-Potassium-Exchanging ATPase