[Reserpine-induced supersensitivity and alpha 1-adrenoceptor subtypes].
Supersensitivity is one of classical and pharmacological phenomena, and may be caused by a variety of procedures, including surgical and chemical denervation and chronic treatment with antagonists. We examined reserpine-induced chemical denervation supersensitivity with special reference to arterial alpha 1-adrenoceptor (alpha 1-AR) subtypes. Chronic treatment with reserpine for 2 weeks produced supersensitivity in the contractile response to phenylephrine of isolated rat tail artery, resulting a leftward shift of concentration-response curve (10 fold shift at EC50 value). This supersensitivity in reserpine-treated artery was selectively inhibited by BMY7378 (alpha 1D-AR selective antagonist) but not by KMD-3213 (alpha 1A-AR selective antagonist). On the other hand, the response to phenylephrine in reserpine-untreated artery was inhibited by KMD-3213 but not by BMY7378. Tissue segment binding study with 3H-prazosin revealed that high affinity binding sites for BMY7378 were detected with a proportion of 32% in reserpine-treated tail artery but absent in untreated artery, although total density of alpha 1-ARs was not changed by reserpine-treatment. The present results strongly suggest that reserpine-induced supersensitivity of rat tail artery is caused by a selective induction of alpha 1D-AR subtype.
Muramatsu
Ikunobu
I
Department of Pharmacology, Fukui Medical University, Matsuoka, Fukui 910-1193, Japan.
Taki
Naoyuki
N
Zhang
Li
L
Israilova
Malika
M
Hiraizumi
Yasuko
Y
Morishima
Shigeru
S
Suzuki
Fumiko
F
Tanaka
Takashi
T
D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001158:Arteries / Q000187:drug effects*; D004361:Drug Tolerance / Q000502:physiology*; D051381:Rats; D018340:Receptors, Adrenergic, alpha-1 / Q000502:physiology*; D012110:Reserpine / Q000494:pharmacology*; D013623:Tail / Q000098:blood supply
D018340:Receptors, Adrenergic, alpha-1; D012110:Reserpine