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Attenuation of Parasite cAMP Levels in T. cruzi ‐Host Cell Membrane Interactions In Vitro
Author(s) -
KREUTER BETSY F.,
WALTON BETH L.,
SANTOSBUCH CHARLES A.
Publication year - 1995
Publication title -
journal of eukaryotic microbiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.067
H-Index - 77
eISSN - 1550-7408
pISSN - 1066-5234
DOI - 10.1111/j.1550-7408.1995.tb01535.x
Subject(s) - biology , receptor , sarcolemma , trypanosoma cruzi , myocyte , muscarinic acetylcholine receptor , membrane , biophysics , cholinergic , microbiology and biotechnology , in vitro , biochemistry , parasite hosting , endocrinology , world wide web , computer science
Previous investigations have shown that the adhesion of T. cruzi plasma membrane vesicles (PMV) to monolayers of host cell myoblasts and to immobilized heart muscle sarcolemma membranes (PAM) on polyaerylamide beads is mediated by the interaction of T. cruzi attachment sites with the muscarinic cholinergic and β‐adrenergic receptors of the host cell membrane. It has also been shown that this interaction is blunted by the specific antagonists of the mammalian receptors atropine and propranol, respectively. In the studies reported here, PAM also rapidly attached to swimming T. cruzi trypomastigotes in a complex, concentration‐dependent fashion and binding isotherms showed that the equilibrium between free and bound PAM is rapidly reached within 2 minutes of incubation in physiologically balanced salt solutions. In this time frame, trypomastigote cAMP levels are significantly reduced from steady state values within 30 seconds of the addition of PAM in a buffer system containing a diesterase inhibitor. Maximal attenuation of cAMP levels was measured between 1 and 2 minutes of the addition of PAM to T. cruzi trypomastigotes. The degree of cAMP level attenuation was reduced by blocking PAM attachment with either atropine or propranol. On the basis of these results we propose that a likely pathway for the negative parasite signal generated upon adhesion of host muscle cell membranes to the surface of the flagellates is from the parasite's surface attachment sites directly to a Pertussis toxin sensitive inhibitory protein G i , thereby blunting adenyl cyclase activity and cAMP formation.