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M H Lam

Publications and source records attributed to M H Lam.

39 records · Page 3Linked to original sources
PubMed1985

Characterization of cutaneous vascular permeability induced by platelet-activating factor in guinea pigs and rats and its inhibition by a platelet-activating factor receptor antagonist.

Mechanisms of platelet-activating factor (PAF)-induced increases of cutaneous vascular permeability in guinea pigs and in rats were further explored. PAF so far is the most potent vasoactive mediator, being more than 1000-fold more potent than histamine and bradykinin in both species. In guinea pigs, there is a time delay of 5 to 10 minutes before PAF action, whereas, in the rat, the increased vasopermeability occurs immediately following the intradermal PAF injection. Relative vasoactive potencies of PAF and several structure-related analogues in both species correlate very well with their relative inhibition of the binding of 3H-PAF to specific receptor sites on isolated rabbit platelet plasma membranes and their aggregatory abilities of rabbit platelets. Furthermore, the PAF-induced cutaneous vascular permeability is inhibitable by a competitive specific PAF receptor antagonist, kadsurenone, suggesting that binding of PAF to its specific receptor site is the first step to initiate its action of increased cutaneous vascular permeability. Several pure cyclooxygenase inhibitors, including indomethacin, diflunisal, and flurbiprofen, and the dual cyclooxygenase/lipoxygenase inhibitor, BW755C, but not the histamine antagonists, inhibit the PAF-induced vasopermeability in guinea pigs. The inhibition by indomethacin or BW755C can be fully reversed by coinjection intradermally with PAF and prostaglandin E1 but not leukotriene B4. Also, prostaglandin E1 but not leukotriene B4 enhances the guinea pig in vivo response to PAF in this model. However, in rats, none of the cyclooxygenase inhibitors, histamine antagonists, or BW755C inhibit the PAF effect of cutaneous phenomena even though prostaglandin E1 also enhances the PAF potency of the increased cutaneous vascular permeability. Kadsurenone, a competitive specific receptor antagonist, inhibits both histamine- and bradykinin-induced rat cutaneous vascular permeability which suggests that PAF may be involved in the vasopermeability induced by histamine and bradykinin.

Animals↗
PubMed1981

Synthetic glycopeptide substrates for receptor-mediated endocytosis by macrophages.

Mammalian macrophages contain a transport system that binds and internalizes glycoproteins with exposed mannose residues. This system and analogous systems on other types of cells require substrates to bear multiple nonreducing terminal residues of the appropriate sugar for effective uptake. Small multivalent synthetic glycopeptides with mannose residues covalently linked through a spacer arm to the alpha- and epsilon-amino groups of lysine, dilysine, and trilysine are competitive inhibitors of rat alveolar macrophage uptake of the neoglycoprotein mannosyl-bovine serum albumin with inhibition constants in the microM range. Various compounds could be covalently attached to the alpha-carboxyl group of these glycopeptides with substantial retention of inhibitory potency. This uptake system does not recognize galactose residues, and the galactosyl analog of an inhibitory mannosylpeptide did not inhibit uptake of mannosyl-bovine serum albumin. The trimannosyldilysine ligand is not only an inhibitor but also a substrate for specific uptake by macrophage, as shown with an 125I-labeled derivative. Macrophages bound 6.4 x 10(5) molecules per cell at 0 degrees C with a dissociation constant of 2 microM. At 21 degrees C the cells could internalize the labeled conjugate with an apparent Michaelis constant of 6 microM and a maximal velocity of 1.7 x 10(5) molecules per min per cel. The dissociation constant and Michaelis constant are similar to the inhibition constant of 9 microM determined at 21 degrees C for inhibition by this conjugate at mannosyl-bovine serum albumin uptake. These synthetic substrates may be useful in targeting pharmacologic agents to macrophages, and analogous compounds may target such agents to other types of cell.

Animals↗