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Pharmacological profiles of CS-932, a functionally selective M1 agonist
S360 AGE-ASSOCIATED
827
CHANGES
SENESCENCE-ACCELERATED KaSAWAl,
NOBUYUKI
KAZUKO
IN THE MONOAMINE
SYNTHESIS SYSTEM IN THE BRAIN OF
MOUSE-PRONE(SAM-P/g)-(B)
WATANABE2,
YOKO YAMAWAKI’,
IKUKO NAGATSU
MINORU ONOZUKA3 lDept. of gnat., Fujita Health Univ. Sch. of Med., Toyoake. 470-l 101, Japan; Depts. of 2Physiology Gifu Univ. Sch of Med., Gifi.r 500-8076, Japan To analyze age-associated changes in monoamine-biosynthesizing months old) and accelerated senescence-resistant
and 3Anat.,
ability, we studied senescence-accelerated
mice (SAM-R/l,8
‘AND
mice (SAM-P/& 8
months old) as controls. We administered,
intraperitoneahy,
2, 4-diamino-&hydroxypyrimidine (DAHP) or parachlorophenylalanine (PCPA) to both groups of mice and measured the time course of changes in dopamine (DA)- immunoreactivity (IR) in the nigrostriatal system, and serotonm (5-HT)- IR in the raphe dorsalis in PAP-stained of SAM-R/l
sections using a microphotometry
was lowest at 3 h after the administration
was lowest at 6 h following
in SAM-R/l
DAHP administration
following PCPA administration
system (Luzex FS, Nicon). While DA-IR in the nigrostriatal system
of DAHP and recovered to normal value 24 h after, that of the SAM-p/8
and did not recover even after 72 h. With respect to 5-HT-IR, while that and recovered 48-72 h after, that in
was lowest at 24 h after the administrauon
SAM-P/8 showed almost no change at 24 h after and decreased slightly 48-72 h after the administrationThese suggest that in SAM-P&while
catecholaminergic
studies strongly
neurons are significantly affected by monoamine synthesis inhibitors,seroto-
nergic neurons do not show significant changes.
828
ALTERATION OF RAT SPINAL CORD GLYCOPROTEIN
YUJI SATO’, YASUKO NAKANO’, ‘Dept. of Glycobiology, Physiological
School of Pharmaceutical
Sciences,
35-2 Sakaecho,
Showa Univ.,
Recently, many evidences of changes of glycans during transformation present study, we examined
whether or not any change
analysis with Lens culinwis agglutinin, elder (29 months old) one.
we compared
and differentiation
of spinal cord glycoprotein
spinal cord glycoproteins
superfamily expression
SAE UCHIDA.
in aging.
In the
By western
blot
of young adult (9 weeks old) rat to those of showed
marked differences.
rat but not in 9-week-old
one.
In
We gave a
Based on amino acid sequence data, gp30 was identified as PO, which is a member
and is the major structural component of mammalian peripheral nerve myelin.
of PO in not only 29-month-old
Taken together, the data indicated that the glycosylated
EFFECTS
Tokyo 142-0064
of the cells accumulated.
occurred
rat but also 9-week-old
rat has been verified.
examined the presence or absence of the sugar moiety of PO from 9-week-old rat, glycosylated
829
Tokyo 173-0015, ‘Dept. of
Shinagawa-ku,
It was found that the reactivity of spinal cord glycoproteins
trivial name, gp30, for this glycoprotein. of the immunoglobulin
Itabashi-ku,
l-5-8 Hatanodai,
particular, a glycoprotein with an apparent Mr 30 KDa was detected in 29-month-old
polyclonal antibody,
AGING
AKIRA KOBATA’, MOTOWO TOMITA2, TAMAO ENDO’
Tokyo Metropolitan Institute of Gerontology,
Chemistry,
DURING
By anti PO When we
PO would not be detected at all.
PO molecule in spinal cord has appeared newly during aging.
OF AGE ON CHOLINERGIC
VASODILATATION
OF CORTlCAL BLOOD FLOW IN RATS.
HARUMI HOTTA, ATSUKO IUMURA
Dept. of Autonomic Nervous System, Tokyo Metropolitan Institute of Gerontology,
Itabashi-ku,
Tokyo 173-0015
Recent work in our laboratory has demonstrated that stimulation of the nucleus basalis of Meynert (NBM) produces increases in both acethylcholine (ACh) release and regional cerebral blood flow (rCBF) in the cortex via activation of both muscarinic The present study sought and nicotinic cholinergic receptors, and this increase in rCBF is reduced significantly in aged rats. to examine age-related changes in the responses of ACh release in the cortex following focal electrical stimulation of the NBM, and the responses of rCBF in the cortex following stimulation of the nicotinic or muscarinic cholinergic receptors by We used three groups of Wistar rats of 3-10 mo old, intravenous (i. v.) administration of nicotine or arecoline, respectively. In 32-36 mo old rats, the increase in rCBF to NBM stimulation was smaller than that in 323-26 mo old and 32-36 mo old. I. v. administration of nicotine, 3 10 mo old rats, while the increase in ACh release in 32-36 mo old rats was well maintained. and 30 pg/?.g, induced dose-dependent increases in rCBF independent of systemic arterial blood pressure in 3-10 mo old rats, Iv. administration of arecoline, 0.06, 0.2 and 0.6 mg/kg, and this increase in rCBF was reduced in 32-36 mo old rats. induced dose-dependent increases in rCBF in 3-10 mo old rats, and this increase in rCBF was well maintained in 32-36 mo old rats. We conclude that nicotinic receptor function in cholinergic vasodilatation of the cortical blood vessels is significantly reduced in aged rats.
827
CHANGES
SENESCENCE-ACCELERATED KaSAWAl,
NOBUYUKI
KAZUKO
IN THE MONOAMINE
SYNTHESIS SYSTEM IN THE BRAIN OF
MOUSE-PRONE(SAM-P/g)-(B)
WATANABE2,
YOKO YAMAWAKI’,
IKUKO NAGATSU
MINORU ONOZUKA3 lDept. of gnat., Fujita Health Univ. Sch. of Med., Toyoake. 470-l 101, Japan; Depts. of 2Physiology Gifu Univ. Sch of Med., Gifi.r 500-8076, Japan To analyze age-associated changes in monoamine-biosynthesizing months old) and accelerated senescence-resistant
and 3Anat.,
ability, we studied senescence-accelerated
mice (SAM-R/l,8
‘AND
mice (SAM-P/& 8
months old) as controls. We administered,
intraperitoneahy,
2, 4-diamino-&hydroxypyrimidine (DAHP) or parachlorophenylalanine (PCPA) to both groups of mice and measured the time course of changes in dopamine (DA)- immunoreactivity (IR) in the nigrostriatal system, and serotonm (5-HT)- IR in the raphe dorsalis in PAP-stained of SAM-R/l
sections using a microphotometry
was lowest at 3 h after the administration
was lowest at 6 h following
in SAM-R/l
DAHP administration
following PCPA administration
system (Luzex FS, Nicon). While DA-IR in the nigrostriatal system
of DAHP and recovered to normal value 24 h after, that of the SAM-p/8
and did not recover even after 72 h. With respect to 5-HT-IR, while that and recovered 48-72 h after, that in
was lowest at 24 h after the administrauon
SAM-P/8 showed almost no change at 24 h after and decreased slightly 48-72 h after the administrationThese suggest that in SAM-P&while
catecholaminergic
studies strongly
neurons are significantly affected by monoamine synthesis inhibitors,seroto-
nergic neurons do not show significant changes.
828
ALTERATION OF RAT SPINAL CORD GLYCOPROTEIN
YUJI SATO’, YASUKO NAKANO’, ‘Dept. of Glycobiology, Physiological
School of Pharmaceutical
Sciences,
35-2 Sakaecho,
Showa Univ.,
Recently, many evidences of changes of glycans during transformation present study, we examined
whether or not any change
analysis with Lens culinwis agglutinin, elder (29 months old) one.
we compared
and differentiation
of spinal cord glycoprotein
spinal cord glycoproteins
superfamily expression
SAE UCHIDA.
in aging.
In the
By western
blot
of young adult (9 weeks old) rat to those of showed
marked differences.
rat but not in 9-week-old
one.
In
We gave a
Based on amino acid sequence data, gp30 was identified as PO, which is a member
and is the major structural component of mammalian peripheral nerve myelin.
of PO in not only 29-month-old
Taken together, the data indicated that the glycosylated
EFFECTS
Tokyo 142-0064
of the cells accumulated.
occurred
rat but also 9-week-old
rat has been verified.
examined the presence or absence of the sugar moiety of PO from 9-week-old rat, glycosylated
829
Tokyo 173-0015, ‘Dept. of
Shinagawa-ku,
It was found that the reactivity of spinal cord glycoproteins
trivial name, gp30, for this glycoprotein. of the immunoglobulin
Itabashi-ku,
l-5-8 Hatanodai,
particular, a glycoprotein with an apparent Mr 30 KDa was detected in 29-month-old
polyclonal antibody,
AGING
AKIRA KOBATA’, MOTOWO TOMITA2, TAMAO ENDO’
Tokyo Metropolitan Institute of Gerontology,
Chemistry,
DURING
By anti PO When we
PO would not be detected at all.
PO molecule in spinal cord has appeared newly during aging.
OF AGE ON CHOLINERGIC
VASODILATATION
OF CORTlCAL BLOOD FLOW IN RATS.
HARUMI HOTTA, ATSUKO IUMURA
Dept. of Autonomic Nervous System, Tokyo Metropolitan Institute of Gerontology,
Itabashi-ku,
Tokyo 173-0015
Recent work in our laboratory has demonstrated that stimulation of the nucleus basalis of Meynert (NBM) produces increases in both acethylcholine (ACh) release and regional cerebral blood flow (rCBF) in the cortex via activation of both muscarinic The present study sought and nicotinic cholinergic receptors, and this increase in rCBF is reduced significantly in aged rats. to examine age-related changes in the responses of ACh release in the cortex following focal electrical stimulation of the NBM, and the responses of rCBF in the cortex following stimulation of the nicotinic or muscarinic cholinergic receptors by We used three groups of Wistar rats of 3-10 mo old, intravenous (i. v.) administration of nicotine or arecoline, respectively. In 32-36 mo old rats, the increase in rCBF to NBM stimulation was smaller than that in 323-26 mo old and 32-36 mo old. I. v. administration of nicotine, 3 10 mo old rats, while the increase in ACh release in 32-36 mo old rats was well maintained. and 30 pg/?.g, induced dose-dependent increases in rCBF independent of systemic arterial blood pressure in 3-10 mo old rats, Iv. administration of arecoline, 0.06, 0.2 and 0.6 mg/kg, and this increase in rCBF was reduced in 32-36 mo old rats. induced dose-dependent increases in rCBF in 3-10 mo old rats, and this increase in rCBF was well maintained in 32-36 mo old rats. We conclude that nicotinic receptor function in cholinergic vasodilatation of the cortical blood vessels is significantly reduced in aged rats.