Endothelin-1 exposure on postnatal day 7 alters expression of the endothelin B receptor and behavioral sensitivity to endothelin-1 on postnatal day 11.
Endothelin (ET)-1 is a chemical mediator released by the body at sites of injury and disease and is involved in various painful states. This study examined whether ET-1 exposure in the neonatal period alters subsequent ET-1 induced nociception and expression of the ET(B) receptor. ET-1 or saline was administered to postnatal day 7 rats. On postnatal day 11, ET-1 or saline was administered; a first exposure to ET-1 for one group, and a second exposure to ET-1 for another group. A statistically significant increase in ET-1 induced paw flinching was observed in postnatal day 11 male rats exposed to ET-1 for the second time as compared to male rats exposed to ET-1 for the first time. In contrast, a statistically significant decrease in ET-1 induced paw flinching was observed in postnatal day 11 female rats exposed to ET-1 for the second time as compared to female rats exposed to ET-1 for the first time. Furthermore, in males a positive correlation was found between ET-1 induced paw flinching on postnatal day 7 versus 11. In contrast, in females a negative correlation was found between ET-1 induced paw flinching on postnatal day 7 versus 11. Changes in behavioral sensitivity to ET-1 were accompanied by sex-specific ET-1 induced changes in expression of the ET(B) receptor on postnatal day 11 in the plantar hind paw with a statistically significant decrease and increase in ET(B) receptor expression in males and females, respectively. These findings suggest that ET-1 exposure in the neonatal period sex-specifically alters expression of the ET(B) receptor and behavioral sensitivity to ET-1 whereby males show sensitization and females show de-sensitization.
McKelvy
Alvin D
AD
Department of Pharmacology, Physiology and Neuroscience, University of South Carolina School of Medicine, 6439 Garner's Ferry Road, Columbia, SC 29208, USA.
Sweitzer
Sarah M
SM
D000375:Aging / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects* / Q000254:growth & development* / Q000378:metabolism; D004361:Drug Tolerance / Q000502:physiology; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D008297:Male; D010146:Pain / Q000139:chemically induced / Q000378:metabolism / Q000503:physiopathology; D010147:Pain Measurement; D017288:Pain Threshold / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects / Q000502:physiology; D044023:Receptor, Endothelin B / Q000187:drug effects* / Q000378:metabolism; D012727:Sex Characteristics
D019332:Endothelin-1; D044023:Receptor, Endothelin B