The inhibitory effect of opioid peptides and morphine applied intrathecally and intracerebroventricularly on the micturition reflex in the cat (original) (raw)

Key words: enkephalins --bladder reflexes --naloxone --morphine --opiate receptors --micturition --DSLET Intrathecal (i.t.) and intracerebroventricular (i.c.v.) administration of enkephalins and enkephalin analogs inhibited reflex contractions of the urinary bladder and firing in vesical parasympathetic postganglionic nerves. Leucine-and methionine-enkephalin (L-Enk and M-Enk, mean threshold doses: 110/~g, i.t. and 17/~g, i.c.v.) elicited short-lasting inhibition (3-30 min), whereas D-Ala2-1eucineand o-Ala2-methionine enkephalinamide (mean threshold dose 23 pg, i.t.), produced more prominent and prolonged inhibition (1.5-3 h). DSLET, a 6 selective opiate receptor agonist, blocked bladder activity when injected i.c.v, or i.t. (mean threshold doses 0.08 gg and 13 gg), whereas morphine, which has greater affinity forg opiate receptors, was effective by i.c.v, and intravenous (i.v.) injection (mean threshold doses, 5 pg and 300 gg/kg), but not by i.t. injection (200--400 #g). Thiorphan (50-200/~g, i.t., i.c.v.) enhanced the responses to L-Enk, whereas naloxone (10-50 pg, i.t., i.c.v., i.v.), blocked the responses to all opioid substances. In untreated animals thiorphan depressed and naloxone enhanced bladder reflexes. With i.t. administration naloxone (10-200 #g) increased the duration and magnitude of bladder contractions, whereas with i.c.v, injections, the drug increased the frequency and reduced the amplitude of the contractions. Large doses of naloxone i.t., but not i.c.v., produced sustained bladder contractions and vesical efferent firing. These results indicate that bladder reflexes are controlled by tonic enkephalinergic inhibitory mechanisms in both the brain and spinal cord. In the brain enkephalinergic inhibition which was mediated by 6 and # opiate receptors, seems to control the frequency of bladder contractions and micturition threshold, whereas in the spinal cord, inhibition is mediated by 6 receptors and seems to control the magnitude of bladder contractions.