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Increase in striatal dopamine D1 and D2 receptor binding by ketamine: Positron emission tomography study using the conscious rhesus monkey
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LIGAND-OATED K ~ CtlANNELS IN CENTRAL NEURONS: SOMATOSTATIN AND ~ - O P I O I D AGONIST ACTIVATED THE S&ME SINGLE K* CtlANNELS. YURI b I I T A N I AND M I C I I I I t l S A bllYAKE, . F a c u l t y of Pharmaceutical Sciences, llokkaido University, Sapporo 060, Japan. Acutely dissociated Locus coeruleus (LC) neurons from new born rats (3-7 days) showed repetitive action potentials and responded to somatostatln (SST) and z -oplold agonist DAGO a s o b s e r v e d in brain slices. We a n a l y z e d single K÷ channel activities recorded from these dissociated LC n e u r o n s in the cellattached mode. The single K÷ c h a n n e l actlvltles Induced b y S S T a n d DAGO w e r e very similar in three aspects. Flrst, these single channels had almost the same magnitude in their unitary conductance. Second, kinetic analysis showed that both channels had one open state and three closed states. Third, the mean open time became longer when higher agonlst concentrations were used, leaving the closed kinetics almost unchanged. As a direct test of the idea that the two different types of agonlst open the same K'channel, we e x a m i n e t h e e f f e c t s of simultaneous application o f SST a n d DAGO o n t h e m e a n o p e n t i m e o f t h e s i n g l e K* channel activities. 0nly longer mean open times were observed in these recordings: the effects were additive. Thus, SST and u -oplold agonlst activated t h e s a m e K° c h a n n e l i n r a t LC n e u r o n s .
Localization of GTP-binding proteins (Gs,Gi,Go)-like immunoreaetivities in t h e r a t brainstem. KOJI OHNO, MAKOTO SATO t, SHINOBU INAGAKI 2, tlIROSHI TAKAGI ~, AND MASAYA T O i l Y A N A t . D e p a r t m e n t o f O t o l a l y n g o l o g y , A n a t o m y 212 O s a k a U n i v e r s i t y Medical School, I-I-50, Fukushimaku, Osaka 553, Japan. Anatomy I, Osaka City University Medical School, I-4-54, Asahicho, Abenoku, Osaka 545, Japan s . The localization of GTP-binding proteins, Gs, Gi a n d Go, w a s e x a m i n e d immunocytochemically using antisera against synthetized the a-subunit of each protein in t h e r a t b r a i n s t e m . S i t e s l a b e l e d b y e a c h a n t i s e r u m w e r e in g e n e r a l similar, though the labeling pattern was d i f f e r e n t among the GTP-binding proteins examined. The following sites were labeled: superficial gray layer of the superior colliculus, dorsal cortex of the inferior colliculus, pontine nucleus, interpeduncular nucleus, locus coeruleus, lateral parabrachial nucleus, mesencephalic trigeminal nucleus, nucleus ambiguus, inferior olive, solitary nucleus, dorsolateral vagus nucleus and spinal trigeminal nucleus. Immunoreactive endproducts f o r Gs w e r e m a i n l y l o c a l i z e d on the cytoplasmic membrane of the s o m a t a , t h o s e f o r Oo w e r e s e e n m a i n l y in t h e n e u r o p i l a n d t h o s e f o r Gi s h o w e d t h e intermediate pattern b e t w e e n Gs a n d Go. T h e s e f i n d i n g s s u g g e s t t h a t Gs i s i n v o l v e d in t h e s y n a p t i c transduction v i a a x o - s o m a t i c s y n a p s e s , w h i l e Go i s i n v o l v e d in t h a t o f a x o - d e n d r i t i c synapses.
INCREASE IN STRIATAL DOPAMINE D1 AND D2 RECEPTOR BINDING BY KETAMINE: POSITRON EMISSION TOMOGRAPHY STUDY USING THE CONSCIOUS RHESUS MONKEY. HIROTAICA- O N O E 1, H I D E O T S U K A D A . 2 , T A I C A S H I I T O * 3 , K A Z U T O S H I S U Z U K I . 4 , M A S A Y U K I K I T A Z U M E . 4 , K A O R U K O B A Y A S H 1 . 4 , N O B U K O M A T A G A 1, O S A M U H A Y A I S H I 1, Y A S U Y O S H I W A T A N A B E 1, O S A M U I N O U E . 4 A N D Y U K I O T A T E N O . 4 , 1 D e p e r t m e n t o f N e u r o s i e n c e , O s a k a B i o s c i e n c e I n s t i t u t e , 6-2-4 F u r u e d a i , S u i t a - s h i , O s a k a 565, 2 C e n t r a l I n s t i t u t e o f H a m a m a t s u P h o t o n i c s K . K . , S h i z u o k a , 3 N i p p o n M e d i c a l School, T o k y o , 4 R e s e a r c h , N a t i o n a l I n s t i t u t e o f R a d i o l o g i c a l S c i e n c g s , Chiba, Japan. Positron emission tomography (PET) is a useful noninvasive technique for analyzing the active sites and biochemical events in specific brain functions by using short-lived radionuelides. Almost all studies using animals were performed under anesthesia and laid on a bed. Recently, to investigate the brain function with PET under conscious and physiological conditions using animals especially monkeys, we have developed a method for stereotaxic fixation of a conscious rhesus monkey in the PET camera with the aid of a special type of chair. We assessed the animal's condition by the use of two dopaminergic receptor ligands, 11C-SC1123390 and N-11C-methylspiperone, for dopamine D1 and D2 receptor bindings, respectively. Intramuscular injection of ketamine (5mg/kg) 30 rain. before the Ugand injection increased the binding activities for D1 and D2 receptors in the striatum. Since MKS01 (100~tg/kg), a more potent noneompetitlve NMDA receptor antagonist, also elevated both receptor bindings, the striatal dopamine D1 and D2 receptor bindings might be regulated by the Ca 2+ channel activity associated with NMDA-type glutamate receptor(s).
LIGAND-OATED K ~ CtlANNELS IN CENTRAL NEURONS: SOMATOSTATIN AND ~ - O P I O I D AGONIST ACTIVATED THE S&ME SINGLE K* CtlANNELS. YURI b I I T A N I AND M I C I I I I t l S A bllYAKE, . F a c u l t y of Pharmaceutical Sciences, llokkaido University, Sapporo 060, Japan. Acutely dissociated Locus coeruleus (LC) neurons from new born rats (3-7 days) showed repetitive action potentials and responded to somatostatln (SST) and z -oplold agonist DAGO a s o b s e r v e d in brain slices. We a n a l y z e d single K÷ channel activities recorded from these dissociated LC n e u r o n s in the cellattached mode. The single K÷ c h a n n e l actlvltles Induced b y S S T a n d DAGO w e r e very similar in three aspects. Flrst, these single channels had almost the same magnitude in their unitary conductance. Second, kinetic analysis showed that both channels had one open state and three closed states. Third, the mean open time became longer when higher agonlst concentrations were used, leaving the closed kinetics almost unchanged. As a direct test of the idea that the two different types of agonlst open the same K'channel, we e x a m i n e t h e e f f e c t s of simultaneous application o f SST a n d DAGO o n t h e m e a n o p e n t i m e o f t h e s i n g l e K* channel activities. 0nly longer mean open times were observed in these recordings: the effects were additive. Thus, SST and u -oplold agonlst activated t h e s a m e K° c h a n n e l i n r a t LC n e u r o n s .
Localization of GTP-binding proteins (Gs,Gi,Go)-like immunoreaetivities in t h e r a t brainstem. KOJI OHNO, MAKOTO SATO t, SHINOBU INAGAKI 2, tlIROSHI TAKAGI ~, AND MASAYA T O i l Y A N A t . D e p a r t m e n t o f O t o l a l y n g o l o g y , A n a t o m y 212 O s a k a U n i v e r s i t y Medical School, I-I-50, Fukushimaku, Osaka 553, Japan. Anatomy I, Osaka City University Medical School, I-4-54, Asahicho, Abenoku, Osaka 545, Japan s . The localization of GTP-binding proteins, Gs, Gi a n d Go, w a s e x a m i n e d immunocytochemically using antisera against synthetized the a-subunit of each protein in t h e r a t b r a i n s t e m . S i t e s l a b e l e d b y e a c h a n t i s e r u m w e r e in g e n e r a l similar, though the labeling pattern was d i f f e r e n t among the GTP-binding proteins examined. The following sites were labeled: superficial gray layer of the superior colliculus, dorsal cortex of the inferior colliculus, pontine nucleus, interpeduncular nucleus, locus coeruleus, lateral parabrachial nucleus, mesencephalic trigeminal nucleus, nucleus ambiguus, inferior olive, solitary nucleus, dorsolateral vagus nucleus and spinal trigeminal nucleus. Immunoreactive endproducts f o r Gs w e r e m a i n l y l o c a l i z e d on the cytoplasmic membrane of the s o m a t a , t h o s e f o r Oo w e r e s e e n m a i n l y in t h e n e u r o p i l a n d t h o s e f o r Gi s h o w e d t h e intermediate pattern b e t w e e n Gs a n d Go. T h e s e f i n d i n g s s u g g e s t t h a t Gs i s i n v o l v e d in t h e s y n a p t i c transduction v i a a x o - s o m a t i c s y n a p s e s , w h i l e Go i s i n v o l v e d in t h a t o f a x o - d e n d r i t i c synapses.
INCREASE IN STRIATAL DOPAMINE D1 AND D2 RECEPTOR BINDING BY KETAMINE: POSITRON EMISSION TOMOGRAPHY STUDY USING THE CONSCIOUS RHESUS MONKEY. HIROTAICA- O N O E 1, H I D E O T S U K A D A . 2 , T A I C A S H I I T O * 3 , K A Z U T O S H I S U Z U K I . 4 , M A S A Y U K I K I T A Z U M E . 4 , K A O R U K O B A Y A S H 1 . 4 , N O B U K O M A T A G A 1, O S A M U H A Y A I S H I 1, Y A S U Y O S H I W A T A N A B E 1, O S A M U I N O U E . 4 A N D Y U K I O T A T E N O . 4 , 1 D e p e r t m e n t o f N e u r o s i e n c e , O s a k a B i o s c i e n c e I n s t i t u t e , 6-2-4 F u r u e d a i , S u i t a - s h i , O s a k a 565, 2 C e n t r a l I n s t i t u t e o f H a m a m a t s u P h o t o n i c s K . K . , S h i z u o k a , 3 N i p p o n M e d i c a l School, T o k y o , 4 R e s e a r c h , N a t i o n a l I n s t i t u t e o f R a d i o l o g i c a l S c i e n c g s , Chiba, Japan. Positron emission tomography (PET) is a useful noninvasive technique for analyzing the active sites and biochemical events in specific brain functions by using short-lived radionuelides. Almost all studies using animals were performed under anesthesia and laid on a bed. Recently, to investigate the brain function with PET under conscious and physiological conditions using animals especially monkeys, we have developed a method for stereotaxic fixation of a conscious rhesus monkey in the PET camera with the aid of a special type of chair. We assessed the animal's condition by the use of two dopaminergic receptor ligands, 11C-SC1123390 and N-11C-methylspiperone, for dopamine D1 and D2 receptor bindings, respectively. Intramuscular injection of ketamine (5mg/kg) 30 rain. before the Ugand injection increased the binding activities for D1 and D2 receptors in the striatum. Since MKS01 (100~tg/kg), a more potent noneompetitlve NMDA receptor antagonist, also elevated both receptor bindings, the striatal dopamine D1 and D2 receptor bindings might be regulated by the Ca 2+ channel activity associated with NMDA-type glutamate receptor(s).