Characterization and function of atp receptors on hepatocytes from
the little skate raja erinacea.
Nathanson, Michael H., and Kavita Mariwalla.
Center for Membrane Toxicity Studies, Mount Desert Island
Biological Laboratory, Salsbury Cove, ME 04672; and Liver Study Unit,
Yale Univ. School of Medicine, New Haven, CT 06520
APStracts 2:0281R, 1995.
Hormonal regulation of hepatocytes, via cytosolic Ca2+ signaling, is
well established in higher life forms but has not been investigated
in elasmobranchs. We therefore ex amined Ca2+ signaling in
hepatocytes isolated from the little skate, Raja erinacea. In
hepatocyte populations, ATP induced a rapid, biphasic increase in
Ca2+, as it does in mammalian hepatocytes. Other hormones that act on
mammalian hepatocytes, including vasopressin, angiotensin, and
phenylephrine, induced no such Ca2+ increase. The initial phase of
the ATP-induced Ca2+ increase was seen even in Ca2+-free medium,
while the late, sustained phase of the increase was not. Similar
dose-response curves were obtained by stimulation with ATP, ADP, UTP,
and 2-methylthio-ATP. In contrast, AMP, adenosine, bg-methyl-ATP, CTP
and GTP induced little or no Ca2+ increase. In single hepatocytes,
ATP, ADP, UTP, and 2-methylthio-ATP each induced a sustained increase
in Ca2+ at high concentrations, but instead induced Ca2+ oscillations
at low concentrations. A maximal concentration of ATP (100 [mu]M)
caused a marked, transient increase in bile flow in the isolated
perfused skate liver, while 100 [mu]M adenosine had no such effect.
These findings demonstrate that skate hepatocytes possess P2
nucleotide receptors that link to intracellular plus extracellular
Ca2+ mobilization, which in turn regulates bile secretion. The broad
specificity of the response to ATP and related compounds suggests
either that multiple types of P2 receptors are expressed by skate
hepatocytes, or else that these cells possess a single, primitive
nucleotide receptor from which other P2 subtypes subsequently
evolved.
Received 12 January 1995; accepted in final form 2 October 1995.
APS Manuscript Number R29-5.
Article publication pending Am. J. Physiol. (Regulatory Integrative
Comp. Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 November 95