Opposite effects of CCK(B) agonists in grooming behaviour in rats: further evidence for two CCK(B) subsites.
1. The hypothesis of the existence of two CCK(B) receptor subsites, CCK(B1) and CCK(B2) corresponding probably to different coupling states of CCK(B) receptors, was studied by measuring grooming behaviour in rats. 2. The B1 receptor agonist, BC197 (300 microg kg(-1), i.p.) produced a 45-50% decrease in grooming activity, which was prevented by both the CCK(B) receptor antagonists CI-988 (20 microg kg(-1) i.p.) and L-365,260 (200 microg kg(-1), i.p.). 3. In contrast, 3, 10 and 30 microg kg(-1), i.p., of the potent B2 receptor agonist, BC264, enhanced grooming (150-190%). This effect was prevented by previous injection of 75 microg kg(-1) of L-365,260 while higher doses (200 microg kg(-1), i.p.) produced only a partial antagonism. Moreover, CI-988 (20 microg kg(-1), i.p.), showed an opposite effect in potentiating the responses induced by BC264. However, 200 microg kg(-1) of CI-988 tended to suppress the increase of grooming induced by BC264. 4. The effects of BC264 were prevented by the D1 receptor (SCH 23390) and D2 receptor (sulpiride) antagonists, while those of BC197 were only antagonized by sulpiride, emphasizing the existence of a link between peptidergic (CCK) and dopaminergic systems. 5. This study brings additional evidence for the existence of the two CCK(B) receptor subsites and suggests that particular attention should be focused on the selectivity of CCK(B) receptor agonists, notably to explain the fact that some compounds such as Boc-CCK4 induce anxiogenic-like effects while others, including BC264, are devoid of these effects.
Département de Pharmacochimie Moléculaire et Structurale, U 266 INSERM, URA D 1500 CNRS, Faculté des Sciences Pharmaceutiques et Biologiques, Paris, France.
N
N
Ladurelle
A
A
Sebret
C
C
Garbay
B P
BP
Roques
V
V
Daugé
D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology; D001665:Binding Sites; D002766:Cholecystokinin / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology; D018491:Dopamine Agonists / Q000494:pharmacology; D006120:Grooming / Q000187:drug effects*; D008297:Male; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin / Q000819:agonists* / Q000378:metabolism; D013469:Sulpiride / Q000494:pharmacology
C084553:BC 264; D001552:Benzazepines; D018491:Dopamine Agonists; D010446:Peptide Fragments; D043887:Receptor, Cholecystokinin B; D011949:Receptors, Cholecystokinin; C060186:BC 197; D013469:Sulpiride; D002766:Cholecystokinin