Tolerance and cross-tolerance to stress-induced increases in plasma Met-enkephalin in rats with adaptively increased resting secretion.
Plasma concentrations of both native (pentapeptide plus its sulfoxide) and peptidase-derivable (trypsin followed by carboxypeptidase-B) Met-enkephalin showed brisk increases in response to the stresses of immobilization, hemorrhage, and electric footshock in conscious, freely moving, adult male rats. Daily exposure to 150-min periods of immobilization resulted in a maintained increase in baseline plasma concentrations of native Met-enkephalin 21.5 h after the sixth day and a further increase after 39 days. The plasma native Met-enkephalin response to acute immobilization was attenuated on day 7 and completely absent on day 40. Unstressed rats showed a plasma native Met-enkephalin response to hemorrhage of 15% blood volume and a further increase in response to 25% hemorrhage. Immediately after initial acute immobilization or 6 days of daily immobilization when plasma native Met-enkephalin was elevated but the response to acute immobilization was attenuated, plasma native Met-enkephalin responses to hemorrhage were also attenuated. Rats that had been immobilized daily for 40 days and showed no plasma native Met-enkephalin response to acute immobilization also showed no responses to hemorrhage. After 39 days of immobilization when there was no plasma native Met-enkephalin response to acute immobilization, there was also no response to footshock. Thus, development of tolerance or adaptive loss of plasma native Met-enkephalin response to immobilization with repeated exposure to this stressor is associated with cross-tolerance or adaptive loss of the responses to the stresses of hemorrhage or electric footshock. Development of tolerance and cross-tolerance of plasma responses of peptidase-derivable Met-enkephalin paralleled that of native Met-enkephalin. Thus, adaptation of plasma Met-enkephalin responses to repeated exposure to a stressor included both increased resting secretion and decreased acute responses to homotypic or novel stressors.
Van Loon
G R
GR
Department of Medicine, University of Kentucky, Lexington.
Pierzchala
K
K
Houdi
A A
AA
Kvetnanský
R
R
Zeman
P
P
D000222:Adaptation, Physiological; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D004361:Drug Tolerance; D004597:Electroshock; D004744:Enkephalin, Methionine / Q000097:blood* / Q000378:metabolism; D005528:Foot; D006470:Hemorrhage / Q000097:blood; D007103:Immobilization; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D012146:Rest; D013312:Stress, Physiological / Q000097:blood* / Q000378:metabolism; D013997:Time Factors
D004744:Enkephalin, Methionine