beta-Casomorphins induce apnea and irregular breathing in adult rats and newborn rabbits.
Bovine beta-casomorphin, beta-casomorphin, morphiceptin or morphine were administered systemically (i.v. or i.p.) and intracerebroventricularly (lateral or IVth ventricles) to anesthetized adult rats and preterm newborn rabbits. All agents caused dose-related depressions of respiratory frequency and tidal volume. Morphiceptin and beta-casomorphin were approximately equipotent to morphine while beta-casomorphin was 10 times as potent after intracerebroventricular injection. The beta-casomorphins decreased inspiratory drive and prolonged the expiratory phase by delaying the setpoint for inspiration. A respiratory depression could be elicited by systemic administration of morphiceptin but not by beta-casomorphin or beta-casomorphin. All ventilatory effects induced by the beta-casomorphins could be readily reversed or prevented by naloxone. Intracerebroventricular but not intraperitoneal injection of beta-casomorphin depressed ventilation in preterm newborn rabbits in a similar pattern with apnoic periods to that seen in the adult rats. In addition, an irregular breathing pattern was elicited. Thus, the bovine beta-casomorphins possess potent central respiratory depressive effects. However, after systemic administration, only morphiceptin which is more metabolically stable induced a shortlasting effect on ventilation in adult rats.
Hedner
J
J
Department of Pharmacology, Gothenburg University, Sweden.
Hedner
T
T
D000595:Amino Acid Sequence; D000818:Animals; D000831:Animals, Newborn; D001049:Apnea / Q000139:chemically induced*; D002417:Cattle; D004723:Endorphins / Q000494:pharmacology*; D006801:Humans; D011817:Rabbits; D012119:Respiration / Q000187:drug effects*
D004723:Endorphins; C021968:beta-casomorphins