Cholera and pertussis toxins increase acidification of endocytic vesicles without altering ion conductances. Van, Rebecca W., Dyke. Gastroenterology Division, Department of Internal Medicine, University of Michigan Medical School and Veterans Administration Medical Center, Ann Arbor, MI 48109-0682
APStracts 3:0363C, 1996.
Acidification of endocytic vesicles, driven by the vacuolar proton pump, is affected by parallel ion transporters. As cAMP and heterotrimeric G proteins may alter ion transporters, we tested whether cholera and pertussis toxins affected acidification of rat liver endosomes. Fluorescein-dextran loaded "10 min" endosomes from cholera toxin treated rats exhibited ATP-dependent rates of acidification in the presence and absence of Cl- or K& that were 60-120% (p<0.05) faster than rates from control endosomes. This increase was greater for "older" "20 min" endosomes and less for "early" "2 min" endosomes. Ion transport functions of "10 min" and "20 min" toxin-exposed endosomes were similar to those of "2 min" control endosomes. Cholera toxin also increased ATP -dependent steady-state intravesicular proton concentration by 38-218% (p<0.05). Pertussis toxin increased endosome acidification rates by 20-54% (p<0.05). Both toxins increased liver cAMP content and endosomes prepared from perfused livers exposed to 0.75 mM dibutyryl cAMP exhibited similar increases in acidification rates. These studies indicate that both cholera and pertussis toxins markedly alter the function of rat liver endosomes. The mechanism is unlikely to reflect major changes in vesicle ion transporters, but rather may indicate either an increase in the number of proton pumps per endosome and/or changes in fusion, remodeling and maturation of early endocytic vesicles in response to cAMP. 

Received 13 August 1996; accepted in final form 8 October 1996.
APS Manuscript Number C460-6.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 31 December 1996