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J. Biol. Chem., Vol. 275, Issue 25, 19115-19120, June 23, 2000
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From the The cholecystokinin (CCK) analog JMV-180 acts as
a partial agonist in rats and a full agonist in mice. Whether this
functional variability is due to species differences in CCK receptor
structure or to alterations in the cellular environment is unknown. To
address this question, an adenoviral construct encoding the rat
CCKA receptor (AdCCKAR) was used to
express the rat receptor in acini from CCKA receptor-deficient mice (CCKAR
Species Differences between Rat and Mouse CCKA
Receptors Determine the Divergent Acinar Cell Response to the
Cholecystokinin Analog JMV-180*
,¶
Department of Physiology, University of
Michigan, Ann Arbor, Michigan 48109-0622 and § Tupper
Research Institute, New England Medical Center,
Boston, Massachusetts 02111
/). Infection of
CCKAR / acini in vitro with
pAdCCKAR led to a time-dependent increase in
125I-CCK8 binding. The affinity for JMV-180 of
the adenovirally transferred rat and the endogenous mouse
CCKA receptors was not different. In native mouse acini,
JMV-180 acted as a full agonist (both stimulation and inhibition
of amylase release). In contrast, in mouse acini expressing
pAdCCKAR JMV-180 acted as a partial agonist (only
stimulation of amylase release). In addition, the pattern of protein
synthesis induced by JMV-180 in CCKAR / mouse acini
infected with AdCCKAR resembled the pattern observed in
wild-type rats (lack of inhibition) rather than the respective pattern
in wild-type mice (inhibition). These data suggest that species
differences in the CCKA receptor of rats and mice account
for the observed divergence in the acinar cell response to JMV-180.
*
This work was supported by National Institutes of Health
Grants DK52067 and DK46767 (to A. S. K.) and University of Michigan Gastrointestinal Peptide Center Grant DK34933.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
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