THE ANTIINFLAMMATORY ACTIVITY OF TOPICALLY APPLIED NOVEL CALCIUM-CHANNEL ANTAGONISTS

被引:11
作者
DEVRIES, GW [1 ]
MCLAUGHLIN, A [1 ]
WENZEL, MB [1 ]
PEREZ, J [1 ]
HARCOURT, D [1 ]
LEE, G [1 ]
GARST, M [1 ]
WHEELER, LA [1 ]
机构
[1] ALLERGAN PHARMACEUT INC,DEPT CHEM SCI,IRVINE,CA 92715
关键词
D O I
10.1007/BF01534466
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
The antiinflammatory activities of two novel calcium-channel antagonists, AGN 190742 and AGN 190744, were evaluated in murine models of cutaneous inflammation. These 2(5H)-furanone ring compounds block both depolarization-dependent Ca2+ entry and receptor-mediated responses in GH3 cells. Topical application of AGN 190742 or AGN 190744 inhibits neutrophil infiltration and epidermal hyperplasia induced by repeated treatment of mouse skin with phorbol ester. AGN 190744 also is active in an arachidonic acid model of acute inflammation. These data suggest that topical application of calcium-channel antagonists can inhibit cutaneous inflammatory responses and that AGN 190742 and/or AGN 190744 may serve as useful pharmacological probes for examining these responses in vivo.
引用
收藏
页码:261 / 275
页数:15
相关论文
共 38 条
[11]   INHIBITION BY MANOALIDE OF FMLP-STIMULATED ELASTASE RELEASE FROM HUMAN NEUTROPHILS [J].
DEVRIES, GW ;
AMDAHL, LD ;
KRAMER, KD ;
WHEELER, LA .
BIOCHEMICAL PHARMACOLOGY, 1990, 40 (11) :2487-2494
[12]   PREFERENTIAL INHIBITION OF 5-LIPOXYGENASE ACTIVITY BY MANOALIDE [J].
DEVRIES, GW ;
AMDAHL, L ;
MOBASSER, A ;
WENZEL, M ;
WHEELER, LA .
BIOCHEMICAL PHARMACOLOGY, 1988, 37 (15) :2899-2905
[13]   INHIBITION OF CUTANEOUS CONTACT HYPERSENSITIVITY BY CALCIUM-TRANSPORT INHIBITORS LANTHANUM AND DILTIAZEM [J].
DIEZEL, W ;
GRUNER, S ;
DIAZ, LA ;
ANHALT, GJ .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 1989, 93 (03) :322-326
[14]  
DUPUIS G, J LEUKOCYTE BIOL, V53, P66
[15]   THE ROLE OF CALCIUM IN NEUTROPHIL MIGRATION - THE EFFECT OF CALCIUM AND CALCIUM-ANTAGONISTS IN ELECTROPORATED NEUTROPHILS [J].
ELFERINK, JGR ;
BOONEN, GJJC ;
DEKOSTER, BM .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1992, 182 (02) :864-869
[16]   FELODIPINE-INDUCED INHIBITION OF POLYMORPHONUCLEAR LEUKOCYTE FUNCTIONS [J].
ELFERINK, JGR ;
DEIERKAUF, M .
BIOCHEMICAL PHARMACOLOGY, 1988, 37 (03) :503-509
[17]   MOLECULAR PHARMACOLOGY OF MANOALIDE - INACTIVATION OF BEE VENOM PHOSPHOLIPASE-A2 [J].
GLASER, KB ;
JACOBS, RS .
BIOCHEMICAL PHARMACOLOGY, 1986, 35 (03) :449-453
[18]   CALCIUM-CHANNEL ANTAGONIST INDUCED-INHIBITION OF SUPEROXIDE PRODUCTION IN HUMAN-NEUTROPHILS - MECHANISMS INDEPENDENT OF ANTAGONIZING CALCIUM INFLUX [J].
IRITA, K ;
FUJITA, I ;
TAKESHIGE, K ;
MINAKAMI, S ;
YOSHITAKE, J .
BIOCHEMICAL PHARMACOLOGY, 1986, 35 (20) :3465-3471
[19]   SOME PHARMACOLOGICAL OBSERVATIONS ON MARINE NATURAL-PRODUCTS [J].
JACOBS, RS ;
CULVER, P ;
LANGDON, R ;
OBRIEN, T ;
WHITE, S .
TETRAHEDRON, 1985, 41 (06) :981-984
[20]  
KRAUSE KH, BLOOD CELLS, V19, P165