P2-purinoceptor localization along a rat nephron and evidence
suggesting the existence of subtype, p2y1 and p2y2.
Cha, Seok Ho, Takashi Sekine, and Hitoshi Endou.
Department of Pharmacology and Toxicology, Kyorin University School
of Medicine, Mitaka, Tokyo 181, Japan. Department of Pharmacology,
Catholic University Medical College,
APStracts 5:0024F, 1998.
Effects of extracellular ATP on intracellular free calcium
concentration ([Ca2+]i) were examined in rat single nephron segments
using the Fura-2/AM. ATP (10 [mu]M) induced a significant transient
increase in [Ca2+]i in the glomerulus, the early proximal convoluted
tubule (S1), the cortical collecting tubule (CCT), and the outer
medullary collecting tubule (OMCT). The magnitude of the response was
the greatest in the OMCT among 4 segments. ATP induced an increase in
the [Ca2+]i in a dose-dependent manner in S1 and OMCT. In the OMCT,
ATP caused a biphasic increase in [Ca2+]i: an initial rapid rise and
a sustained phase. Removal of calcium from the medium resulted in an
attenuation of the sustained phase of [Ca2+]i and an 30% reduction in
the height of the initial [Ca2+]i peak in response to 10 [mu]M ATP.
Effects of ATP, its analogs, and its metabolites were tested in the
S1 and OMCT. ATP, 2-methylthio(MeS)-ATP, ADP, and UTP increased
[Ca2+]i dose-dependently. AMP and adenosine did not affect [Ca2+]i in
the S1 and OMCT. ATP- or 2-MeS-ATP-induced [Ca2+]i increase was
inhibited by the pretreatment of the S1 and OMCT with suramin or
reactive blue 2. Neomycin, a phospholipase C inhibitor, attenuated
the ATP-induced [Ca2+]i increase. To investigate the hormone-like
action of ATP in OMCT, a heterologous cross desensitization was
performed. The pretreatment of OMCT with ATP inhibited increases in
vasopressin-, angiotensin II-, endothelin I- or bradykinin-induced
[Ca2+]i increase. These findings suggest that ATP might affect the
above peptidyl agonist-activated calcium mobilizations.
Received 21 Augst 1995; accepted in final form 26 January 1998.
APS Manuscript Number F278-5.
Article publication pending Am. J. Physiol. (Renal Physiology).
ISSN 1080-4757 Copyright 1998 The American Physiological Society.
Published in APStracts on 28 January 1998