Respiratory effects of beta-endorphin, D-Ala2-met-enkephalinamide, and Met-enkephalin injected into the lateral ventricle and the pontomedullary subarachnoid space.

The respiratory effects of Met-enkephalin (900 microgram), D-Ala2-Met-enkephalinamide (10 microgram), and beta-endorphin (10 microgram) were studied and compared in lightly anesthetized cats, after injection into the lateral ventricle and into the pontomedullary subarachnoid space. The 3 peptides injected into the lateral ventricle induced equidepressant effects on respiration, but the duration of action and the involvement of either frequency or tidal volume varied considerably. Met-enkephalin was shorter-acting (45 min) than both D-Ala2-Met-enkephalinamide and beta-endorphin (over 5 h). The depression induced by beta-endorphin was preceded by a long-lasting stimulation of frequency. The effects were antagonized by i.v. naloxone, but the antagonism was not complete in one third of the animals. In the pontomedullary subarachnoid space, beta-endorphin failed to depress respiration significantly whereas Met-enkephalin induced an immediate and short-acting depression (15 min), and D-Ala2-Met-enkephalinamide depressed respiration for 2-4 h in a biphasic pattern. It is concluded that: (1) respiration is depressed by the 3 opiate peptides; (2) the effects of beta-endorphin on respiration, at the dose used in this study, are secondary to other actions on higher brain structures; and (3) Met-enkephalin and D-Ala2-Met-enkephalinamide seem to affect pontomedullary areas located near the ventral surface, although they may also interact with respiratory structures located more deeply in the brain stem.