title: Interaction between D2 dopaminergic and glutamatergic excitatory influences on lower urinary tract function in normal and cerebral-infarcted rats.
abstract: Previous studies showed that bladder hyperactivity after cerebral infarction in Sprague-Dawley (SD) rats was mediated in part by D2 dopaminergic and NMDA glutamatergic mechanisms. In the present experiments, the interaction between dopaminergic and glutamatergic excitatory mechanisms in the control of bladder and external urethral sphincter (EUS) reflexes was investigated in urethane-anesthetized sham-operated (SO) and cerebral-infarcted (CI) SD rats. Occlusion of the left middle cerebral artery or a sham operation was performed under halothane anesthesia. Two hours after either of the two procedures, rats were anesthetized with urethane. Dizocilpine, an N-methyl-d-aspartate (NMDA) glutamatergic antagonist, was administered intravenously in doses of 0.3 or 3 mg/kg to CI rats and 3 mg/kg to SO rats. These doses completely inhibited bladder and EUS activity. The effects of apomorphine (a dopamine agonist with greater efficacy at D2 than D1 receptors) or quinpirole (a selective D2 dopamine receptor agonist) were examined on the dizocilpine-induced depression of bladder contractions and EUS EMG activity. Apomorphine did not antagonize the dizocilpine depression of EUS activity, but it did reestablish the micturition reflex after dizocilpine blockade and did increase the amplitude of bladder contractions and voided volume in a dose-dependent manner (0.0001-10 mg/kg, iv), in both CI rats and SO rats pretreated with dizocilpine. There were no differences between SO rats and CI rats in the apomorphine responses in rats pretreated with doses of 0.3 or 3 mg/kg dizocilpine. A larger dose of dizocilpine (10 mg/kg) did not affect the bladder contractions after apomorphine administration. Quinpirole (0.001-1 mg/kg, iv) also partially reversed the dizocilpine depression of bladder activity in SO and CI rats. These results indicate that NMDA glutamatergic and D2 dopaminergic mechanisms exert independent excitatory influences on bladder activity in both SO and CI rats. D2 dopamine receptor agonists can reverse the effect of NMDA receptor blockade on bladder activity but were ineffective in reversing the block of sphincter activity.
authors: Department of Pharmacology, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, 15261, USA.
authors: O
authors: O
authors: Yokoyama
authors: M
authors: M
authors: Yoshiyama
authors: M
authors: M
authors: Namiki
authors: W C
authors: WC
authors: de Groat
mesh_terms: D000758:Anesthesia; D000818:Animals; D001058:Apomorphine / Q000008:administration & dosage; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D018491:Dopamine Agonists / Q000008:administration & dosage; D018492:Dopamine Antagonists / Q000008:administration & dosage; D065127:Dopamine D2 Receptor Antagonists; D004305:Dose-Response Relationship, Drug; D004576:Electromyography / Q000187:drug effects; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D005260:Female; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology*; D007275:Injections, Intravenous; D009119:Muscle Contraction / Q000187:drug effects; D019257:Quinpirole / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D017448:Receptors, Dopamine D2 / Q000819:agonists*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D012018:Reflex / Q000187:drug effects / Q000502:physiology; D013469:Sulpiride / Q000008:administration & dosage; D001743:Urinary Bladder / Q000187:drug effects / Q000503:physiopathology; D014551:Urinary Tract / Q000187:drug effects / Q000503:physiopathology*
chemical_list: D018491:Dopamine Agonists; D018492:Dopamine Antagonists; D065127:Dopamine D2 Receptor Antagonists; D018691:Excitatory Amino Acid Antagonists; D017448:Receptors, Dopamine D2; D016194:Receptors, N-Methyl-D-Aspartate; D019257:Quinpirole; D016291:Dizocilpine Maleate; D013469:Sulpiride; D001058:Apomorphine