T sub 84 cell receptor binding and guanyl cyclase activation by Escherichia coli heat-stable toxin

Journal Article · Tue Dec 01 00:00:00 EST 1987 · American Journal of Physiology; (USA)

OSTI ID:6994886

Guarino, A; Cohen, M; Thompson, M; Dharmsathaphorn, K; Giannella, R ^[1]

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1. Veterans Administration Hospital, Cincinnati, OH (USA) Univ. of Cincinnati, OH (USA) Univ. of California, San Diego (USA)

Escherichia coli heat-stable enterotoxin (STa) induces intestinal secretion by binding to enterocyte receptors and activating the guanylate cyclase-guanosine 3{prime},5{prime}-cyclic monophosphate (cGMP) system. The intermediate steps between binding of STa and secretion are poorly understood, due in part to the lack of a convenient system to study the effects of STa at the cellular level. To establish such a model, the authors investigated the binding of {sup 125}I-STa, STa activation of guanylate cyclase, and STa-induced increase in cGMP production in a well-characterized human colonic cell line, T{sub 84}. Binding was specific, linear with cell number, and time, temperature and pH dependent, and reversible. ST may also be internalized by these cells. Addition of unlabeled STa competitively inhibited binding of {sup 125}I-STa. These parameters closely resemble those described in intact rat enterocytes and cell-free membrane preparations. STa stimulated guanylate cyclase and cGMP production in a dose-related manner. The similar dose-response relationships for binding, guanylate cyclase stimulation by STa, and cGMP production suggest that the guanylate cyclase-cGMP system is coupled to ST occupancy of specific receptors. These data, together with the fact that STa induces chloride secretion from T{sub 84} cells suggest that T{sub 84} cells are a suitable and convenient system to study the cellular mechanism of action of STa.

• OSTI ID: 6994886
• Journal Information: American Journal of Physiology; (USA), Vol. 253:6; ISSN 0002-9513
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
CYCLASES
ENZYME INDUCTION
DIARRHEA
PHYSIOLOGY
RECEPTORS
BIOCHEMICAL REACTION KINETICS
TOXINS
BIOLOGICAL EFFECTS
DOSE-RESPONSE RELATIONSHIPS
ESCHERICHIA COLI
GUANINE
IODINE 125
SECRETION
AMINES
ANTIGENS
AROMATICS
AZAARENES
BACTERIA
BETA DECAY RADIOISOTOPES
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ENZYMES
GENE REGULATION
HETEROCYCLIC COMPOUNDS
HYDROXY COMPOUNDS
INTERMEDIATE MASS NUCLEI
IODINE ISOTOPES
ISOTOPES
KINETICS
LYASES
MATERIALS
MEMBRANE PROTEINS
MICROORGANISMS
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
PROTEINS
PURINES
RADIOISOTOPES
REACTION KINETICS
SYMPTOMS
TOXIC MATERIALS
550201* - Biochemistry- Tracer Techniques