Effect of (+/-)-epibatidine, a nicotinic agonist, on the central pathways controlling voiding function in the rat.
Nicotinic receptors in the brain modulate the release of many transmitters that are known to regulate voiding. This prompted us to examine the central nervous system effects of a neuronal nicotinic agonist, (+/-)-epibatidine, on voiding function in awake and anesthetized rats. Intracerebroventricular injection of (+/-)-epibatidine (0.1 microg) significantly increased intercontraction interval (ICI) but did not change pressure threshold (PT) or maximal voiding pressure (MVP), whereas 1 microg of (+/-)-epibatidine increased PT and MVP (P < 0.05) and decreased ICI. A low intravenous dose of (+/-)-epibatidine (0.001-0.1 microg) had no effect; however, a large dose of (+/-)-epibatidine (1 microg) significantly decreased ICI and increased MVP (P < 0.05) but did not change PT (P > 0.05). The effects occurred within 5-10 min after injection and persisted for 1-2 h. Intracerebroventricular chlorisondamine (10 microg), a nicotinic receptor antagonist, blocked the effect of intracerebroventricular (+/-)-epibatidine (0.1 microg). The experiments revealed that activation of nicotinic receptors in the brain increased bladder capacity in awake and anesthetized rats. These results suggest that the nicotinic agonist can activate mechanisms that inhibit voiding reflexes.
Lee
Sun-Ju
SJ
Dept. of Pharmacology, Univ. of Pittsburgh School of Medicine, 200 Lothrop St., E1303 Biomedical Science Tower, Pittsburgh, Pennsylvania, 15261. sjlee@khu.ac.kr
Nakamura
Yasuo
Y
de Groat
William C
WC
D018686:Anesthetics, Intravenous; D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology*; D002714:Chlorisondamine / Q000494:pharmacology; D005260:Female; D007276:Injections, Intraventricular; D018733:Nicotinic Antagonists / Q000494:pharmacology*; D011725:Pyridines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011978:Receptors, Nicotinic / Q000502:physiology*; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D014520:Urethane; D001743:Urinary Bladder / Q000294:innervation / Q000502:physiology*; D014554:Urination / Q000187:drug effects / Q000502:physiology*; D014851:Wakefulness
D018686:Anesthetics, Intravenous; D019086:Bridged Bicyclo Compounds, Heterocyclic; D018733:Nicotinic Antagonists; D011725:Pyridines; D011978:Receptors, Nicotinic; D014520:Urethane; D002714:Chlorisondamine; C082748:epibatidine