Characterization of distinct phospholipases mediating bradykinin and noradrenaline hyperalgesia.
Specific prostaglandins have been identified that mediate the sympathetic postganglionic neuron-terminal dependent hyperalgesia induced by bradykinin and norepinephrine, prostaglandin E2 and prostacyclin, respectively. In this study we evaluated the hypothesis that bradykinin and norepinephrine stimulate prostaglandin production in the rat, via distinct phospholipases. We found that, in normal skin, bradykinin hyperalgesia is inhibited by the phospholipase A2 inhibitor, mepacrine, but not by the phospholipase C inhibitor, neomycin and is mimicked by phospholipase A2. In chloroform-treated skin or when co-injected with A23187, bradykinin-induced hyperalgesia was found to consist of two components, one resulting from prostaglandin E2 synthesis (phospholipase A2-dependent) and one resulting from prostacyclin synthesis (phospholipase C-dependent). This latter component is blocked by Quin 2 and verapamil and also inhibited by yohimbine, an alpha 2 receptor antagonist. Arachidonic acid induces a dose-dependent hyperalgesia that was found to be like bradykinin-hyperalgesia in untreated skin (prostaglandin E2-mediated and phospholipase A2-dependent). In chloroform-treated skin or in the presence of A23187, arachidonic acid like bradykinin led to the production of prostacyclin as well as prostaglandin E2. Norepinephrine does not produce hyperalgesia in untreated skin, but in chloroform pretreated skin or in the presence of the calcium ionophore A23187, norepinephrine produces a potent dose-dependent hyperalgesia. This hyperalgesia is prevented by sympathectomy and suppressed by the calcium antagonists Quin 2 and verapamil. It is also suppressed by indomethacin and neomycin but not by SC19220 and mepacrine and is mimicked by phospholipase C.(ABSTRACT TRUNCATED AT 250 WORDS)
Taiwo
Y O
YO
Department of Anatomy, University of California, San Francisco 94143-0724.
Heller
P H
PH
Levine
J D
JD
D000634:Aminoquinolines / Q000494:pharmacology; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000494:pharmacology*; D001920:Bradykinin / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D005456:Fluorescent Dyes; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D009355:Neomycin / Q000494:pharmacology*; D009619:Nociceptors / Q000187:drug effects / Q000502:physiology; D009638:Norepinephrine / Q000494:pharmacology*; D010741:Phospholipases A / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054467:Phospholipases A2; D011796:Quinacrine / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000187:drug effects / Q000201:enzymology*; D010738:Type C Phospholipases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D014700:Verapamil / Q000494:pharmacology
D000634:Aminoquinolines; D001095:Arachidonic Acids; D005456:Fluorescent Dyes; D016718:Arachidonic Acid; D000001:Calcimycin; D014700:Verapamil; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D011796:Quinacrine; D009355:Neomycin; C035739:Quin2; D001920:Bradykinin; D009638:Norepinephrine