Corticotropin-releasing factor inhibits neurogenic plasma extravasation in the rat paw.
Increased exudation of plasma proteins, as measured by Evans blue leakage into the innervated paw, was produced by antidromic stimulation of the saphenous nerve in the pentobarbital-anesthetized rat. This condition, termed neurogenic plasma extravasation (NPE), was inhibited by morphine, FK 33,824 (a stabilized enkephalin analog), dynorphin (1-13), dynorphin(1-10)amide and corticotropin-releasing factor (CRF) at median effective doses of 2700, 0.45, 1180, 4050 and 5.6 nmol/kg i.v., respectively. The inhibitory effect of CRF was present when injected up to 60 min before electrical stimulation of the nerve. By contrast, the effects of morphine and FK 33,824 were shorter in duration, lasting for only 20 to 30 min before nerve stimulation. Inhibition of NPE by morphine, FK 33,824 dynorphin (1-13) and dynorphin (1-10)amide was blocked by naloxone, 1 mg/kg i.v., but the CRF inhibition was not affected. CRF inhibited NPE in both hypophysectomized and adrenalectomized rats, indicating that its effects were not due to secondary release of endogenous opioid peptides. The inhibitory effect of CRF on NPE was also separable from its hypotensive properties and could be obtained at intradermal doses of CRF into the paw skin which were approximately 11 times lower than the i.v. doses. Intracerebroventricular injection of CRF did not affect the tail-flick latency of rats to warm water. CRF administered i.v. in mice did, however, inhibit writhing responses to phenylbenzoquinone (PBQ), suggesting possible peripheral antinociceptive properties.
D000315:Adrenalectomy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin / Q000494:pharmacology; D004399:Dynorphins / Q000494:pharmacology; D004558:Electric Stimulation; D007016:Hypophysectomy; D008297:Male; D009020:Morphine / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains
D005405:D-Ala(2),MePhe(4),Met(0)-ol-enkephalin; D004399:Dynorphins; D009020:Morphine; D003346:Corticotropin-Releasing Hormone