Local regulation of skin blood flow during cooling involving presynaptic P2 purinoceptors in rats.
1. This study investigated a local effect of cooling on the plantar skin blood flow (PSBF) of tetrodotoxin-treated rats by laser-Doppler flowmetry. 2. When the air temperature around the left foot was locally cooled from 25 to 10 degrees C, the PSBF of the left foot decreased. 3. The response was inhibited by the alpha-adrenoceptor antagonist phentolamine, the alpha1-adrenoceptor antagonist bunazosin, the alpha2-adrenoceptor antagonist RS79948, and bretylium and guanethidine that inhibit noradrenaline release from sympathetic nerves. Adrenalectomy of the rats did not affect the cooling-induced response. 4. The P2 purinoceptor antagonists suramin and PPADS also significantly suppressed the cooling-induced reduction of PSBF. However, the inhibitory effect of PPADS on the cooling-induced response was abolished after the treatment with phentolamine. Intra-arterial injections of ATPgammaS, a stable P2 purinoceptor agonist, at 25 degrees C caused a transient decrease in PSBF in a dose-dependent manner, which was significantly inhibited by phentolamine and guanethidine. 5. These results suggest a novel mechanism for local cooling-induced reduction of skin blood flow in vivo; moderate cooling of the skin induces the release of ATP, which stimulates presynaptic P2 purinoceptors on sympathetic nerve terminals and facilitates the release of noradrenaline, thereby causing contractions of skin blood vessels via the activation of alpha1-and alpha2-adrenoceptors.
Koganezawa
Tadachika
T
Department of Cellular and Molecular Pharmacology, Graduate School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka City, Shizuoka 422-8526, Japan.
Ishikawa
Tomohisa
T
Fujita
Yukiyoshi
Y
Yamashita
Tomonari
T
Tajima
Takako
T
Honda
Masaki
M
Nakayama
Koichi
K
D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000502:physiology; D001833:Body Temperature Regulation / Q000502:physiology*; D003080:Cold Temperature; D005528:Foot / Q000098:blood supply; D008297:Male; D008833:Microcirculation / Q000187:drug effects / Q000502:physiology; D017729:Presynaptic Terminals / Q000502:physiology; D058919:Purinergic P2 Receptor Antagonists; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017661:Receptors, Presynaptic / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000502:physiology*; D012039:Regional Blood Flow / Q000502:physiology*; D012867:Skin / Q000098:blood supply*; D012881:Skin Temperature / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology
D058919:Purinergic P2 Receptor Antagonists; D017661:Receptors, Presynaptic; D018048:Receptors, Purinergic P2; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D013498:Suramin