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The receptor occupation and plasma concentration of NKY‐722, a water‐soluble dihydropyridine‐type calcium antagonist, in spontaneously hypertensive rats
Author(s) -
Uchida S.,
Yamada S.,
Ohkura T.,
Heshikiri M.,
Yoshimi A.,
Shirahase H.,
Kimura R.
Publication year - 1995
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1995.tb14928.x
Subject(s) - antagonist , calcium , dihydropyridine , endocrinology , medicine , chemistry , pharmacology , receptor
1 The occupation in vivo by NKY‐722 of 1,4‐dihydropyridine (DHP) calcium antagonist receptors in myocardium, aorta and cerebral cortex was investigated. At 1 and 3 h after oral administration of NKY‐722 (3 mg kg −1 ) in spontaneously hypertensive rats (SHR), there was a significant (44 and 41%, respectively) decrease in the number of myocardial (+)‐[ 3 H]‐PN 200‐110 binding sites ( B max ) compared to control values. A greater reduction of B max values was observed at 1 (86%), 3 (88%), 6 (63%) and 12 (46%) h later by a higher dose (10 mg kg −1 ) of this drug. The occupation of myocardial 1,4‐DHP calcium antagonist receptors after oral administration of NKY‐722 correlated significantly with its plasma concentration. There was a significant decrease in cerebral cortical (+)‐[ 3 H]‐PN 200‐110 binding ( B max ) at 1 and 3 h after oral administration of NKY‐722 (10 mg kg −1 ). 2 Oral administration of nicardipine (10 mg kg −1 ) in SHR caused a significant reduction of B max values for (+)‐[ 3 H]‐PN 200‐110 binding in myocardium at 1 and 3 h later and in cerebral cortex at 1 h later. 3 The in vivo specific binding of (+)‐[ 3 H]‐PN 200‐110 in particulate fractions of aorta of SHR was significantly (79 and 83%, respectively) reduced at 1 and 6 h after oral administration of NKY‐722 (3 mg kg −1 ), while myocardial (+)‐[ 3 H]‐PN 200‐110 binding was decreased by 52% only at 1 h later. Also, nicardipine administration reduced in vivo (+)‐[ 3 H]‐PN 200‐110 binding in aorta at 1 and 6 h later and in myocardium at 1 h later. On the other hand, the administration of both NKY‐722 and nicardipine had no significant effect on in vivo (+)‐[ 3 H]‐PN 200‐110 binding in cerebreal cortex. 4 It is concluded that NKY‐722 may exert more selective and sustained occupation in vivo of 1,4‐DHP calcium antagonist receptors in vascular tissues of SHR than in myocardial and brain tissues.