Hormone receptor gradients supporting directional Ca2+ signals: direct evidence in rat hepatocytes.
OBJECTIVE
In the liver, InsP(3)-dependent agonists such as vasopressin and noradrenaline induce tightly coordinated sequences of intracellular Ca(2+) increases, leading to apparent unidirectional Ca(2+) waves. In previous works, we have postulated that cell-to-cell differences in hormone receptor density create a cellular sensitivity gradient that determines which cell initiates the intercellular Ca(2+) wave and the direction of propagation of the Ca(2+) signal. The aim of this study was to test directly this hypothesis.


METHODS
Lobular distribution of V1a vasopressin receptors and alpha1 adrenergic receptors were observed by autoradiography in rat liver sections. Cell-to-cell differences in the number of these receptors were evaluated on hepatocyte multiplets using specific fluorescent probes.


RESULTS
The relative amount of fluorescence associated with the V1a receptor differed significantly between cells within multiplets. The 'cell-after-cell' Ca(2+) increase induced by vasopressin was correlated with the number of V1a receptors. These observations may be more general, as autoradiography revealed similar lobular distributions of V1a receptors and alpha1 adrenergic receptors; the amounts of both were greatest in hepatocytes surrounding central veins.


CONCLUSIONS
These data confirm that a fine gradient along liver cell plates contributes to the molecular basis of the unidirectional hormone-induced Ca(2+) signalling observed in the liver lobule.
Clair
Caroline
C
Institut National de la Santé et de la Recherche Médicale Unité U442, Université de Paris-Sud, Bât 443, 91405 Orsay, France.
Tran
Dien
D
Boucherie
Sylviane
S
Claret
Michel
M
Tordjmann
Thierry
T
Combettes
Laurent
L
D000818:Animals; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000502:physiology*; D002462:Cell Membrane / Q000378:metabolism; D005260:Female; D022781:Hepatocytes / Q000378:metabolism*; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D009994:Osmolar Concentration; D051381:Rats; D017208:Rats, Wistar; D018340:Receptors, Adrenergic, alpha-1 / Q000378:metabolism*; D017483:Receptors, Vasopressin / Q000378:metabolism*; D014018:Tissue Distribution; D014667:Vasopressins / Q000494:pharmacology
D018340:Receptors, Adrenergic, alpha-1; D017483:Receptors, Vasopressin; D014667:Vasopressins; D002118:Calcium