Epinephrine exacerbates arthritis by an action at presynaptic B2-adrenoceptors.
Sympathetic efferents contribute to the severity of joint injury in experimental arthritis in the rat, [Levine J. D. et al. (1986) J. Neurosci. 6, 3423-3429] and beta 2-adrenergic receptor antagonists suppress the disease [Levine J. D. et al. (1988) Proc. natn. Acad. Sci. U.S.A. 85, 4553-4556]. The present study was directed at determining the endogenous ligand for, and target of, the beta 2-receptor contribution to arthritis. We report that adrenal medullectomy significantly reduced joint injury in experimental arthritis, but that severe joint injury was re-established in adrenal medullectomized rats chronically treated with epinephrine or the beta 2-agonist, salbutamol. The ability of these two drugs to enhance joint injury in adrenal medullectomized rats was blocked by sympathectomy. These data suggest that adrenal medulla-derived epinephrine acts at beta 2-adrenoceptors on sympathetic efferent nerve terminals, to contribute to the severity of experimental arthritis.
Coderre
T J
TJ
Department of Medicine, University of California, San Francisco 94143-0724.
Basbaum
A I
AI
Dallman
M F
MF
Helms
C
C
Levine
J D
JD
D000313:Adrenal Medulla / Q000378:metabolism* / Q000503:physiopathology; D000320:Adrenergic Fibers / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D001168:Arthritis / Q000378:metabolism* / Q000503:physiopathology; D004837:Epinephrine / Q000494:pharmacology / Q000502:physiology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects / Q000502:physiology*; D013562:Sympathectomy
D011943:Receptors, Adrenergic, beta; D004837:Epinephrine