Selective inhibitory effects of ethylketocyclazocine on reflex pathways to the external urethral sphincter of the cat.
In the ventral horn of the sacral spinal cord of the cat, opioid terminals are preferentially localized in Onuf's nucleus, an area containing motor neurons that innervate the striated muscle of the external urethral sphincter. The present study was undertaken to 1) compare the effects of selective opioid agonists on sphincter reflex pathways with the effects of these drugs on hindlimb reflexes and urinary bladder reflexes and 2) determine if the physiological inhibition of sphincter reflexes, which accompany bladder contractions, is mediated by endogenous opioids. The effects of intrathecal (i.t.) and i.v. drug administration on bladder activity, sphincter reflexes and reflexes to the hindlimb musculature were monitored in chloralose-anesthetized cats. Ethylketocyclazocine (0.05-500 micrograms i.t.) produced a dose-dependent, naloxone-sensitive, inhibition of sphincter reflexes to less than 10% of control amplitude while having no consistent effects on hindlimb reflexes or bladder activity. D-Ser2-leu5-enkephalin-thr6 (DSLET; 0.1-2.0 micrograms i.t.) abolished rhythmic bladder activity, while having no effects on sphincter or hindlimb reflexes. Larger doses of DSLET (5.0-10 micrograms i.t.) produced a modest reduction of sphincter reflexes (to 60% of control amplitude), without affecting hindlimb reflexes. Naloxone (50 micrograms i.t.) reversed DSLETs marked inhibition of bladder activity, whereas large doses (greater than 250 micrograms i.t.) only partially antagonized DSLETs weak inhibition of sphincter reflexes. Morphine (5-500 micrograms i.t.) had no consistent effect on any of the measures.(ABSTRACT TRUNCATED AT 250 WORDS)
Thor
K B
KB
Department of Pharmacology, University of Pittsburgh School of Medicine, Pennsylvania.
Hisamitsu
T
T
Roppolo
J R
JR
Tuttle
P
P
Nagel
J
J
deGroat
W C
WC
D000818:Animals; D002415:Cats; D003496:Cyclazocine / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D004743:Enkephalin, Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D016308:Enkephalin, Leucine-2-Alanine; D016314:Ethylketocyclazocine; D005260:Female; D009020:Morphine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D011957:Receptors, Opioid / Q000187:drug effects; D017473:Receptors, Opioid, kappa; D012018:Reflex / Q000187:drug effects*; D014521:Urethra / Q000187:drug effects* / Q000502:physiology; D001743:Urinary Bladder / Q000187:drug effects / Q000502:physiology; D014549:Urinary Incontinence / Q000188:drug therapy
D009842:Oligopeptides; D011957:Receptors, Opioid; D017473:Receptors, Opioid, kappa; D009270:Naloxone; D016314:Ethylketocyclazocine; D004743:Enkephalin, Leucine; D016308:Enkephalin, Leucine-2-Alanine; C034318:enkephalin, Ser(2), Leu(5), Thr(6)-; D009020:Morphine; D003496:Cyclazocine