Abstract
Ion transport in the jejunal mucosa of 14- to 16-day-old piglets with severe diarrhea 40hr after infection with transmissible gastroenteritis (TGE) virus was studied. In infected pigs Na+ transport failed to. respond normally to glucose when studied either in Ussing short-circuited chambers or in suspensions of enterocytes isolated selectively from jejunal villi. Theophylline, 10 mm, added to the chambers produced the same brisk electrical responses and increments in net Cl− secretion in tissue from both infected and control groups. A defect in glucose-stimulated Na+ absorption in the acute stage of a viral enteritis has been identified which probably contributes to the impaired lumen-to-extracellular fluid flux of Na+ found previously in the jejunum of intact TGE-infected pigs. The mechanisms causing diarrhea in this invasive viral enteritis differ from those causing toxigenic diarrhea.
Footnotes
This study was supported by grants from the Medical Research Council of Canada and the Pathfinder Foundation.
The authors with to express their appreciation to Drs. StanleySchultz, Raymond Frizzell, Hugh Nellands, and B. G. Munck for advice in setting up the Ussing chamber and for thoughtful criticism on the progress of the experiments, and to Dr. Ron Hancock for the donation of the 24Na. These experiments depended on the skilled and dedicated technical assistance of Mr. M. Khan, Mrs. Piya Drew, Miss Dianne Chapman, and Mrs. M. Perdue.
References
- 1.Tajima M. Morphology of transmissible gastroenteritis virus of pigs. A possible member of corona viruses. Arch Gesamte Virusforsch. 1970;29:105–108. doi: 10.1007/BF01253886. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Haelterman EO, Hooper BE. Transmissible gastroenteritis of swine as a model for the study of enteric disease. Gastroenterology. 1967;53:109–113. [PubMed] [Google Scholar]
- 3.Pensaert M, Haelterman EO, Burnstein T. Transmissible gastro-enteritis of swine: Virus-intestinal cell interactions. I. Immuno-fluorescence, histopathology and virus production in the small intestin. Arch Gesamte Virusforsch. 1970;31:321–351. doi: 10.1007/BF01253767. [DOI] [PubMed] [Google Scholar]
- 4.Haelterman EO. On the pathogenesis of transmissible gastroenteritis of swine. J Am Vet Med Assoc. 1972;160:534–540. [PubMed] [Google Scholar]
- 5.Kelly M, Butler DG, Hamilton JR. Transmissible gastroenteritis in piglets: a model of infantile viral diarrhea. J Pediatr. 1972;80:925–931. doi: 10.1016/S0022-3476(72)80003-9. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Butler DG, Gall DG, Kelly MH. transmissible gastroenteritis: mechanisms responsible for diarrhea in an acute viral enteritis in piglets. J Clin Invest. 1974;53:1335–1342. doi: 10.1172/JCI107681. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 7.Hooper BE, Haelterman EO. Growth of transmissible gastroenteritis virus in young pigs. Am J Vet Res. 1966;27:286–291. [PubMed] [Google Scholar]
- 8.Clarkson TW, Toole SR. Measurement of short-circuit current and ion transport across the ileum. Am J Physiol. 1964;206:658–668. [Google Scholar]
- 9.Asano T. Metabolic disturbances and short-circuit current across intestinal wall of rat. Am J Physiol. 1964;207:415–422. doi: 10.1152/ajplegacy.1964.207.2.415. [DOI] [PubMed] [Google Scholar]
- 10.Schultz SG, Zalusky R. Ion transport in isolated rabbit ileum. I. Short-circuit current and Na fluxes. J Gen Physiol. 1964;47:567–584. doi: 10.1085/jgp.47.3.567. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11.Gall DG, Butler DG, Tepperman F. Sodium ion transport in isolated intestinal epithelial cells: the effect of actively transported sugars on sodium ion efflux. Biochim Biophys Acta. 1974;339:291–302. doi: 10.1016/0005-2736(74)90156-4. [DOI] [PubMed] [Google Scholar]
- 12.Munck BG. Effects of sugar and amino acid transport on transepi-thelial fluxes of sodium and chloride of short-circuited rat jejunum. J Physiol (Lond) 1972;223:699–717. doi: 10.1113/jphysiol.1972.sp009870. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 13.Fromm D. Na and Cl transport across isolated proximal small intestine of the rabbit. Am J Physiol. 1973;224:110–116. doi: 10.1152/ajplegacy.1973.224.1.110. [DOI] [PubMed] [Google Scholar]
- 14.Binder HJ. Sodium transport across isolated human jejunum. Gastroenterology. 1974;67:231–236. [PubMed] [Google Scholar]
- 15.Rohde JE, Anderson B. In vitro measurement of ion fluxes across biopsies of human jejunal mucosa during cholera. J Appl Physiol. 1973;35:557–561. doi: 10.1152/jappl.1973.35.4.557. [DOI] [PubMed] [Google Scholar]
- 16.Field M, Fromm D, Al-Awgati Q. Effect of cholera enterotoxin on ion transport across isolated ileal mucosa. J Clin Invest. 1972;51:796–804. doi: 10.1172/JCI106874. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Field M. Ion transport in rabbit ileal mucosa. II. Effects of cyclic 3′, 5′-AMP. Am J Physiol. 1971;221:992–997. doi: 10.1152/ajplegacy.1971.221.4.992. [DOI] [PubMed] [Google Scholar]
- 18.Al-Awgati Q, Cameron JL, Greenough WB., III Electrolyte transport in human ileum: effect of purified cholera exotoxin. Am J Physiol. 1973;224:818–823. doi: 10.1152/ajplegacy.1973.224.4.818. [DOI] [PubMed] [Google Scholar]
- 19.Al-Awgati Q, Wallace CK, Greenough WB., III Stimulation of intestinal secretion in vitro by culture filtrates of Escherichia coli. J Infect Dis. 1972;125:300–303. doi: 10.1093/infdis/125.3.300. [DOI] [PubMed] [Google Scholar]
- 20.Al-Awgati Q, Garcia-Bunuel R, Field M. The influence of structural abnormality on ion transport in rabbit ileum. Proc Soc Exp Biol Med. 1970;135:598–604. doi: 10.3181/00379727-135-35103. [DOI] [PubMed] [Google Scholar]
- 21.Fromm D, Gianella RA, Formal SB. Ion transport across isolated mucosa invaded by salmonella. Gastroenterology. 1974;66:215–225. [PubMed] [Google Scholar]
- 22.Bishop RF, Davidson GP, Holmes IH. Virus particles in epithelial cells of duodenal mucosa from children with acute non-bacterial gastroenteritis. Lancet. 1973;2:1281–1283. doi: 10.1016/s0140-6736(73)92867-5. [DOI] [PubMed] [Google Scholar]
- 23.Middleton PJ, Szymanski MT, Abott GD. Orbi virus acute gastroenteritis of infancy. Lancet. 1974;1:1241–1244. [Google Scholar]
- 24.Flewett TJ, Bryden AS, Davies H. Relation between viruses from acute gastroenteritis of children and newborn calves. Lancet. 1974;2:61–63. doi: 10.1016/s0140-6736(74)91631-6. [DOI] [PubMed] [Google Scholar]
- 25.Kapikian AZ, Kim HW, Wyatt RG. Reovirus-like agent in 1964 stool: association with infantile diarrhea and development of serologic tests. Science. 1974;185:1049–1053. doi: 10.1126/science.185.4156.1049. [DOI] [PubMed] [Google Scholar]
- 26.Davidson GP, Townley RRW, Bishop RF. Importance of a new virus in acute sporadic enteritis in children. Lancet. 1975;1:242–246. doi: 10.1016/s0140-6736(75)91140-x. [DOI] [PubMed] [Google Scholar]