Abstract

Direct administration of either oxytocin or its analogue (1-penicillamine,4-threonine)oxytocin into the preoptic anterior hypothalamus caused hyperthermia in conscious rats at ambient temperatures ( T a's) of 8, 22 and 30°C. At a T a of 8°C, the hyperthermia was solely brought about by an increase in metabolic rate. At a T a of 22°C, the hyperthermia was brought about by both an increase in metabolism and a decrease in cutaneous temperature. At a T a of 30°C, the hyperthermia was due to solely to decrease in cutaneous temperature. There was no change in respiratory evaporative heat loss in response to these drugs at all temperatures tested. Intrahypothalamic injection of either isoproterenol or phenylephrine also produced hyperthermia, increased metabolism and cutaneous constriction. In addition, the hyperthermia induced by intrahypothalamic injection of oxytocin or its analogue was antagonized by pretreatment with intrahypothalamic injection of sodium acetylsalicylate (an inhibitor of prostaglandin E synthetase) or yohimbine (an antagonist of alpha-adrenergic receptors) but not with propanolol (antagonist of beta-adrenergic receptors). The data indicate that a prostaglandin-adrenergic link in the hypothalamus is involved in the hyperthermia induced by oxytocin or its analogue. Furthermore, the oxytocin-induced hyperthermia was antagonized by pretreatment with a small dose of (1-penicillamine,4-threonine)oxytocin. On the other hand, the hyperthermia induced by (1-penicillamine,4-threonine)oxytocin was also antagonised by pretreatment with a small dose of oxytocin. Thus, it appears that (1-penicillamine,4-threonine)oxytocin is an anti-oxytocin analogue which inhibits the hyperthermic activity of oxytocin.

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