Abstract
Behavioral and receptor binding techniques were employed to evaluate the potency of CR 1409, a new analog of proglumide, as a cholecystokinin antagonist. CR 1409, at doses of 1 mg/kg i.p. in mice, effectively blocked the inhibition of feeding and exploratory behaviors induced by cholecystokinin. In rats, CR 1409 alone, at doses of 1 and 10 mg/kg, did not affect feeding or exploratory behaviors, but at 25 mg/kg alone, CR 1409 reduced food intake and exploratory behaviors, suggesting a mixed agonist-antagonist profile. On these several behavorial parameters, CR 1409 antagonized peripherally administered cholecystokinin with 10-1000 times greater potency than that reported for proglumide (Crawley et al., J. Pharmac. Exp. Ther. 236, 320-330, 1986). In binding to pancreatic cholecystokinin membranes, CR 1409 was more than 100,000-times more potent than that reported for proglumide (Rovati, Scand. J. Gastroenterol. 11, 113-118, 1976). CR 1409 inhabited binding of 125-I-cholecystokinin octapeptide in mouse parcreatic and brain membranes with IC50 values of 13.7 nM and 2.6 μM, respectively, demonstrating its selectivity for peripheral-type CCK receptors.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 547-553 |
| Number of pages | 7 |
| Journal | Neurochemistry International |
| Volume | 10 |
| Issue number | 4 |
| DOIs | |
| State | Published - 1987 |
| Externally published | Yes |
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ASJC Scopus subject areas
- Cell Biology
- Molecular Biology
- Cellular and Molecular Neuroscience
Cite this
Potency of CR 1409, a new proglumide analog, on cholecystokinin-mediated behaviors and receptor binding. / Kaltwasser, Maria Th; Petrack, Barbara; Crawley, Jacqueline.
In: Neurochemistry International, Vol. 10, No. 4, 1987, p. 547-553.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Potency of CR 1409, a new proglumide analog, on cholecystokinin-mediated behaviors and receptor binding
AU - Kaltwasser, Maria Th
AU - Petrack, Barbara
AU - Crawley, Jacqueline
PY - 1987
Y1 - 1987
N2 - Behavioral and receptor binding techniques were employed to evaluate the potency of CR 1409, a new analog of proglumide, as a cholecystokinin antagonist. CR 1409, at doses of 1 mg/kg i.p. in mice, effectively blocked the inhibition of feeding and exploratory behaviors induced by cholecystokinin. In rats, CR 1409 alone, at doses of 1 and 10 mg/kg, did not affect feeding or exploratory behaviors, but at 25 mg/kg alone, CR 1409 reduced food intake and exploratory behaviors, suggesting a mixed agonist-antagonist profile. On these several behavorial parameters, CR 1409 antagonized peripherally administered cholecystokinin with 10-1000 times greater potency than that reported for proglumide (Crawley et al., J. Pharmac. Exp. Ther. 236, 320-330, 1986). In binding to pancreatic cholecystokinin membranes, CR 1409 was more than 100,000-times more potent than that reported for proglumide (Rovati, Scand. J. Gastroenterol. 11, 113-118, 1976). CR 1409 inhabited binding of 125-I-cholecystokinin octapeptide in mouse parcreatic and brain membranes with IC50 values of 13.7 nM and 2.6 μM, respectively, demonstrating its selectivity for peripheral-type CCK receptors.
AB - Behavioral and receptor binding techniques were employed to evaluate the potency of CR 1409, a new analog of proglumide, as a cholecystokinin antagonist. CR 1409, at doses of 1 mg/kg i.p. in mice, effectively blocked the inhibition of feeding and exploratory behaviors induced by cholecystokinin. In rats, CR 1409 alone, at doses of 1 and 10 mg/kg, did not affect feeding or exploratory behaviors, but at 25 mg/kg alone, CR 1409 reduced food intake and exploratory behaviors, suggesting a mixed agonist-antagonist profile. On these several behavorial parameters, CR 1409 antagonized peripherally administered cholecystokinin with 10-1000 times greater potency than that reported for proglumide (Crawley et al., J. Pharmac. Exp. Ther. 236, 320-330, 1986). In binding to pancreatic cholecystokinin membranes, CR 1409 was more than 100,000-times more potent than that reported for proglumide (Rovati, Scand. J. Gastroenterol. 11, 113-118, 1976). CR 1409 inhabited binding of 125-I-cholecystokinin octapeptide in mouse parcreatic and brain membranes with IC50 values of 13.7 nM and 2.6 μM, respectively, demonstrating its selectivity for peripheral-type CCK receptors.
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UR - http://www.scopus.com/inward/citedby.url?scp=0023184934&partnerID=8YFLogxK
U2 - 10.1016/0197-0186(87)90083-0
DO - 10.1016/0197-0186(87)90083-0
M3 - Article
AN - SCOPUS:0023184934
VL - 10
SP - 547
EP - 553
JO - Neurochemistry International
JF - Neurochemistry International
SN - 0197-0186
IS - 4
ER -