Perfusion of the fourth cerebral ventricle with the synthetic opioid peptide, FK 33-824, induces dose-related bradycardia and naloxone-reversible respiratory depression in the awake dog

Abstract

The importance of natural opioids in the central control of blood pressure, heart rate and respiratory function was evaluated with a synthetic analogue of Met-enkephalin, FK 33-824, which is more resistant to enzymatic degradation than the natural opioids. Increasing concentrations (20, 100, 200 and 400 micrograms/ml), perfused through the 4th cerebral ventricle of the conscious dog, induced a concentration-related depression of respiratory function - as reflected in arterial pCO2 and pO2 and heart rate. Naloxone (40 micrograms/ml) was able to reverse respiratory depression whereas bradycardia was naloxone-resistant even after massive (100 micrograms/kg) intravenous doses. Mean arterial blood pressure was not affected in the tested concentration range. Because respiration was reversed by naloxone, it is concluded that respiratory control is regulated by the mu-type opioid receptor. Heart rate, however, may be governed by the delta-type opioid receptor which is less susceptible to naloxone.