On the mechanisms of action of PAF on the myocardium. 1991

M Gollasch, and V B Ignatieva, and E M Kobrinsky, and E G Vornovitsky
Institute of Physiology, Humboldt-University, Berlin, Germany.

The effects of PAF (1-2 X 10(-7) M) on intracellular slow Ca-mediated action potentials (Ca-AP) and isometric contractions of guinea-pig auricle muscles and ionic currents of frog atrial trabeculae were investigated. PAF decreased the amplitude, duration and upstroke velocity of the slow Ca-AP mediated via the L-type Ca channels in guinea-pig auricle muscles without changes in the resting potential. The PAF receptor antagonist U-66985 (1-5 X 10(-6) M), histamine (10(-4) M) and 4-aminopyridine (3 mM) inhibited the depressant effects of PAF on the slow AP and contractions. PAF reduced the peak of the slow inward Ca current (ICa) via the L-type Ca channels of frog atrial trabeculae. Simultaneously, the delayed outward K current (IK) was increased by PAF. Pretreatment with the PAF receptor antagonist BN 52021 (4 X 10(-6) M) protected the effects of PAF on ICa and IK. Our data demonstrate both by direct and indirect methods of ICa registration an inhibiting effect of PAF on the ICa via the L-type Ca channels and make probable a similarity in PAF signalling in cardiac cells of cold- and warm-blooded animals. The coupling of changes of the ICa with the augmentation of IK accentuate the important role of myocardial L-type Ca and K channels in mediating the negative inotropic action of PAF. The ability of U-66985 and BN 52021 to inhibit the electrophysiological effects of PAF hint at a membrane signalling coupled by specific binding sites for PAF in the myocardium.

UI MeSH Term Description Entries
D007783 Lactones Cyclic esters of hydroxy carboxylic acids, containing a 1-oxacycloalkan-2-one structure. Large cyclic lactones of over a dozen atoms are MACROLIDES. Lactone
D009200 Myocardial Contraction Contractile activity of the MYOCARDIUM. Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D010972 Platelet Activating Factor A phospholipid derivative formed by PLATELETS; BASOPHILS; NEUTROPHILS; MONOCYTES; and MACROPHAGES. It is a potent platelet aggregating agent and inducer of systemic anaphylactic symptoms, including HYPOTENSION; THROMBOCYTOPENIA; NEUTROPENIA; and BRONCHOCONSTRICTION. AGEPC,Acetyl Glyceryl Ether Phosphorylcholine,PAF-Acether,Phosphorylcholine, Acetyl Glyceryl Ether,1-Alkyl-2-acetyl-sn-glycerophosphocholine,Platelet Aggregating Factor,Platelet Aggregation Enhancing Factor,Platelet-Activating Substance,Thrombocyte Aggregating Activity,1 Alkyl 2 acetyl sn glycerophosphocholine,Aggregating Factor, Platelet,Factor, Platelet Activating,PAF Acether,Platelet Activating Substance
D011895 Rana ridibunda A species of the family Ranidae which occurs primarily in Europe and is used widely in biomedical research.
D002118 Calcium A basic element found in nearly all tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes. Coagulation Factor IV,Factor IV,Blood Coagulation Factor IV,Calcium-40,Calcium 40,Factor IV, Coagulation
D004224 Diterpenes Twenty-carbon compounds derived from MEVALONIC ACID or deoxyxylulose phosphate. Diterpene,Diterpenes, Cembrane,Diterpenes, Labdane,Diterpenoid,Labdane Diterpene,Norditerpene,Norditerpenes,Norditerpenoid,Cembranes,Diterpenoids,Labdanes,Norditerpenoids,Cembrane Diterpenes,Diterpene, Labdane,Labdane Diterpenes
D006168 Guinea Pigs A common name used for the genus Cavia. The most common species is Cavia porcellus which is the domesticated guinea pig used for pets and biomedical research. Cavia,Cavia porcellus,Guinea Pig,Pig, Guinea,Pigs, Guinea
D006321 Heart The hollow, muscular organ that maintains the circulation of the blood. Hearts
D006632 Histamine An amine derived by enzymatic decarboxylation of HISTIDINE. It is a powerful stimulant of gastric secretion, a constrictor of bronchial smooth muscle, a vasodilator, and also a centrally acting neurotransmitter. Ceplene,Histamine Dihydrochloride,Histamine Hydrochloride,Peremin
D000200 Action Potentials Abrupt changes in the membrane potential that sweep along the CELL MEMBRANE of excitable cells in response to excitation stimuli. Spike Potentials,Nerve Impulses,Action Potential,Impulse, Nerve,Impulses, Nerve,Nerve Impulse,Potential, Action,Potential, Spike,Potentials, Action,Potentials, Spike,Spike Potential

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