Hisako Yamagishi1,2,*, Masahito Watanabe1,3, Kinya
Yazaki1,2, Kohei Sawaki1,2 and Mitsuru Kawaguchi1,2
Departmentﾊof Pharmacology and 2Oral Health Science Center,
Tokyo Dental College,
1-2-2 Masago, Mihamaku, Chiba 261-8502, Japan
3Environmentﾊ& Safety Research Department, Research & Development
Division,
Nihon Bayer Agrochem K.K., Yuki Research Center, 9511-4, Yuki, Yuki-shi,
Ibaraki 307-0001, Japan
*ﾊTo whom correspondence should be addressed(1).
Abstract: Pharmacological characterization of peripheral type
benzodiazepine receptors in rat, rabbit, mouse and human salivary glands
was determined by receptor binding and photoaffinity labeling analysis using
[3H]PK14105 (1-(2-fluoro-5-nitrophenyl)-3-isoquinolinecarboxylic
acid). [3H]PK14105 bound to the membranes of salivary glands
in rats, rabbits, mice and humans with high affinity at the nanomolar level.
The rank order of receptor density in submandibular glands among several
species was as follows: humanﾊ³ﾊratﾊ³ﾊmouse>ﾊrabbit.
Competitive potency of receptor ligands against [3H]PK14105 was
as follows: PK11195ﾊ³ﾊRo5-4864>ﾊdiazepamﾊ>ﾊclonazepamﾊ>ﾊRo15-1788.
The rank order of potency against calcium channel ligands and co-transport
inhibitors was as follows: nitrendipineﾊ>ﾊBAYﾊKﾊ8644ﾊ>ﾊbumetanideﾊ>ﾊfurosemide.
Pretreatment with nitrendipine or BAYﾊKﾊ8644 decreased the affinity of [3H]PK14105
binding to rat parotid gland membranes, without changing the density. The
photoaffinity labeling with [3H]PK14105 indicated the presence
of the 18-kDa protein in all salivary glands of our experiment. The inhibition
of photolabeling by some receptor ligands was the same results as the receptor
binding assay. In conclusion, the peripheral type benzodiazepine receptors
include the 18-kDa protein photolabeled with [3H]PK14105 in salivary
glands of rat, mouse, rabbit and human.
Keywords: Peripheral type benzodiazepine receptor, Salivary gland, Photoaffinity
labeling, [3H]PK14105