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Galanin Reduces Carbachol Stimulation of Phosphoinositide Turnover in Rat Ventral Hippocampus by Lowering Ca 2+ Influx Through Voltage‐Sensitive Ca 2+ Channels
Author(s) -
Palazzi E.,
Felinska S.,
Zambelli M.,
Fisone G.,
Bartfai T.,
Consolo S.
Publication year - 1991
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1991.tb01986.x
Subject(s) - carbachol , stimulation , galanin , hippocampus , chemistry , biophysics , endocrinology , medicine , neuroscience , neuropeptide , biology , biochemistry , receptor
The 29‐amino‐acid peptide galanin (GAL) caused concentration‐dependent inhibition of the accumulation of 3 H‐inositol phosphates ( 3 H‐InsPs) induced by the muscarinic agonist carbachol (CARB; 10 ‐3 ‐10 ‐5 M ) in the presence of 5 m M lithium, specifically in tissue miniprisms from rat ventral hippocampus. The inhibitory effect of GAL involved the mono‐, bis‐, tris‐, and tetrakisphosphates formed during activation for 2 min of phospholipase C by CARB (1 m M ) in the absence of lithium. GAL (1 μ M ) did not affect α‐adrenergic or serotonergic type 2 receptor‐mediated phosphoinositide (PI) breakdown in the same tissue. GAL by itself neither acted on basal levels of 3 H‐InsPs nor affected muscarinic receptors in binding studies. Blockade of the T‐, N‐, and L‐types of voltage‐sensitive calcium channel (VSCC) with 200 μ M Cd 2+ reduced muscarinic receptor‐mediated PI breakdown by 50% and abolished the inhibitory effect of GAL (1 μM). Reduction of the extracellular Ca 2+ concentration from 1.3 m M to 0.49 μ M abolished the GAL inhibition of CARB‐stimulated PI hydrolysis. Ca 2+ influx promoted by 18 m M K + depolarization or by 1 μ M Bay K 8644, a selective agonist of the L‐type VSCC, prevented the inhibitory effect of GAL. Blockade of the L‐type VSCC with nifedipine (1 μ M ) potentiated the inhibitory effects of GAL without affecting muscarinic stimulation of PI breakdown. The neurotoxin ω‐conotoxin (2 μ M ), a blocker of both L‐ and N‐types of VSCC, by itself reduced CARB‐mediated breakdown of PIs by ∼25%, and when it was added before GAL (1 μ M ) there was no summation of the two individual inhibitory effects, a result suggesting a common site of action for GAL and ω‐conotoxin. The data presented thus indicate that GAL modulation of muscarinic stimulation of the phospholipase C activity is mediated by a reduction of Ca 2+ entry through VSCCs, presumably of the N type.