1989 Fiscal Year Final Research Report Summary
Biochemical studies on interaction between muscarinic acetylcholine receptors and somatostatin in the brain
| Project/Area Number |
62440036
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| Research Category |
Grant-in-Aid for General Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Research Field |
内科学一般
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| Research Institution | HIROSHIMA UNIVERSITY |
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Principal Investigator |
KITO Shozo Hiroshima Univ. School of Medicine, Professor, 医学部, 教授 (00010140)
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| Co-Investigator(Kenkyū-buntansha) |
MIYOSHI Rie Hiroshima Univ. School of Medicine, Research Associate, 医学部, 助手 (80209965)
SHIMOYAMA Masanori Hiroshima Univ. School of Medicine, Assistant Professor, 医学部, 講師 (60136067)
YAMAMURA Yasuhiro Hiroshima Univ. Medical Hospital, Assistant Professor, 医学部・付属病院, 講師 (10106388)
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| Project Period (FY) |
1987 – 1989
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| Keywords | Mammalian central nervous system / Neurotranmitter receptors / Neuropeptide / Neuropharmacology / Muscarinic acetylcholine receptors / Somatostatin / Intracellular calcium concentration |
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| Research Abstract |
Modulatory effects of neuropeptides on classic type of neurotransmission were investigated in the rat central nervous system, with emphasis on an interaction between muscarinic acetylcholine receptors (mAChR) and somatostatin. Somatostatin decreased the affinity of mAChR in the hippocampus, and the effect of this peptide was limited to agonist binding to MI subtype. Somatostatin augmented phosphatidylinositol (PI) turnover stimulated by mAChR activation, while the peptide itself had no effect on PI turnover. To elucidate a mechanism for somatostatin's action, an intracellular response of somatostatin receptors was examined in the hippocampus. Although it has been considered that somatostatin acts as a inhibitory neuropeptide in the central and peripheral tissues, we noticed that the peptide increased intracellular Ca^<2+> concentration ([Ca^<2+>]i) in cultured rat hippocampal neurons. The source of Ca^<2+> for somatostatin's effect was an influx from extracellular fluids, not mediated by PI turnover. Since omega-conotoxin GVIA inhibited the effect of somatostatin, it seems that somatostatin receptors are coupled with N-type Ca^<2+> channels in the rat hippocampus. It is suggested that the rise of [Ca^<2+>]i is an important key point for modulating the function of mAChR. As another example of modulation of neurotransmitter receptors by neuropeptides, we studied the effect of cholecystokinin (CCK) on dopamine Dl receptors in the rat striatum. CCK-8 did not affect an antagonist binding site of Di receptors, whereas it reduced the affinity of agonist binding. As for intracellular response of CCK receptors, an increase of [Ca^<2+>]i was observed by CCK stimulation, not mediated by PI turnover like the case of somatostatin. From above-mentioned experimental data, it is considered that modulatory effect of neuropeptide on classical neurotransmission is something like a common pathway and there is no difference among the peptides.
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