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  • Title: The inhibitory effect of opioid peptides and morphine applied intrathecally and intracerebroventricularly on the micturition reflex in the cat.
    Author: Hisamitsu T, de Groat WC.
    Journal: Brain Res; 1984 Apr 23; 298(1):51-65. PubMed ID: 6586255.
    Abstract:
    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 micrograms, i.t. and 17 micrograms, i.c.v.) elicited short-lasting inhibition (3-30 min), whereas D-Ala2-leucine- and D-Ala2-methionine enkephalinamide (mean threshold dose 23 microgram, i.t.), produced more prominent and prolonged inhibition (1.5-3 h). DSLET , a delta selective opiate receptor agonist, blocked bladder activity when injected i.c.v. or i.t. (mean threshold doses 0.08 microgram and 13 micrograms), whereas morphine, which has greater affinity for mu opiate receptors, was effective by i.c.v. and intravenous (i.v.) injection (mean threshold doses, 5 micrograms and 300 micrograms/kg), but not by i.t. injection (200-400 micrograms). Thiorphan (50-200 micrograms, i.t., i.c.v.) enhanced the responses to L-Enk, whereas naloxone (10-50 micrograms, 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 micrograms) 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 versical 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 delta and mu opiate receptors, seems to control the frequency of bladder contractions and micturition threshold, whereas in the spinal cord, inhibition is mediated by delta receptors and seems to control the magnitude of bladder contractions.
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