Release from inflamed tissue of a substance with properties similar to corticotropin-releasing factor.
In response to stressors involving tissue injury, pituitary corticotroph secretion of immunoreactive beta-endorphin (iB-END) could be either due to release of hypothalamic factors such as corticotropin-releasing factor (CRF) or to release of a tissue factor from the periphery. In the present experiments, we investigated whether inflamed tissue releases a factor which evokes pituitary secretion of iB-END. In an initial experiment, rats with an inflamed hindpaw due to carrageenan injection had significantly greater levels of circulating iB-END as compared to rats with saline-injected paws. Removal of afferent input, by hindlimb denervation, failed to block the carrageenan-induced increase in iB-END levels. Subcutaneous perfusates were then collected from inflamed and control hindlimbs and applied to rat anterior pituitary cell cultures. Pituitary release of iB-END due to administration of perfusate from inflamed paws was significantly greater than iB-END release due to perfusate from saline-injected paws or to basal release. The releasing activity in the perfusates was blocked in calcium-free medium and was not due to a direct action of carrageenan, bradykinin, substance P or calcitonin gene-related peptide. The results indicate that inflamed tissue releases a CRF-like factor which stimulates iB-END release both in the denervated rat and cultured pituitary cells.
Hargreaves
K M
KM
Neurobiology and Anesthesiology Branch, National Institute of Dental Research, Bethesda, Md.
Costello
A H
AH
Joris
J L
JL
D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002351:Carrageenan; D002851:Chromatography, High Pressure Liquid; D003346:Corticotropin-Releasing Hormone / Q000378:metabolism*; D003714:Denervation; D006614:Hindlimb / Q000294:innervation; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D011863:Radioimmunoassay; D051381:Rats; D011919:Rats, Inbred Strains; D001615:beta-Endorphin / Q000378:metabolism
D001615:beta-Endorphin; D002351:Carrageenan; D003346:Corticotropin-Releasing Hormone; D002118:Calcium