Modulation of Trypanosoma cruzi adhesion to host muscle cell membranes by ligands of muscarinic cholinergic and beta adrenergic receptors.
Plasma membrane vesicles (PMVs) of Trypanosoma cruzi adhered to L6 myoblast host cells as a function of time and concentration in saturation phenomena in a similar fashion to that reported in a previous publication. The initial adhesion rate (A0) of T. cruzi PMVs to L6 myoblasts in tissue culture was inhibited by acetylcholine (10(-5) M), isoproterenol (10(-5) M) and norepinephrine (10(-8) M) (range 29.1-50.3% of control). Atropine, the antagonist of muscarinic cholinergic receptors (10(-5) M), and propranolol or pindolol, the antagonists of beta-adrenergic receptors (10(-5) M), were also equal inhibitors of the T. cruzi PMV to L6 myoblast adhesion rate (range 26.1 to 55.5% of control). The alpha-adrenergic receptor ligands yohimbine and phentolamine (10(-5) M) showed no A0 inhibitory activity in similar assays. The interaction of T. cruzi PMVs with type I host muscle sarcolemma receptors was clearly defined in assays which used porcine heart atrial membranes (PAMs) immobilized on cationic polyacrylamide beads. In this parasite membrane-host cell membrane assay system, 10(-10) M atropine and 5 x 10(-9) M propranolol produced a shift of an S-shaped T. cruzi PMV to PAM saturation isotherm to the right, suggesting that a negative cooperative interaction was produced between the intramembrane ligand binding site and another, surface heterotropic T. cruzi PMV adhesion site. Atropine and propranolol were equieffective inhibitors of the T. cruzi striated muscle sarcolemma recognition process, raising the possibility that T. cruzi attachment molecules annexed pairs of muscarinic cholinergic and beta-adrenergic receptors to effect adhesion of the two membrane surfaces.
von Kreuter
B F
BF
Department of Pathology, Cornell University Medical College, New York, NY 10021.
Santos-Buch
C A
CA
D000318:Adrenergic beta-Agonists / Q000494:pharmacology*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000818:Animals; D002448:Cell Adhesion; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000469:parasitology; D008956:Models, Chemical; D011941:Receptors, Adrenergic / Q000187:drug effects / Q000502:physiology*; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000502:physiology*; D012508:Sarcolemma / Q000187:drug effects / Q000378:metabolism* / Q000469:parasitology; D013552:Swine; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000378:metabolism*
D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D011941:Receptors, Adrenergic; D011976:Receptors, Muscarinic