Galanin inhibits adenylate cyclase of rat brain membranes

doi:10.1016/0196-9781(92)90118-M

Peptides

Volume 13, Issue 2, March–April 1992, Pages 339-341

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Abstract

The ubiquitous neuropeptide, galanin, strongly inhibits adenylate cyclase in rat brain membranes. While basal enzyme activity was not altered, galanin from 10⁻¹¹ M to $5×10^{−7} M$ decreased forskolin- and VIP-stimulated adenylate cyclase with a half-maximal effect being elicited by 0.7 nM neuropeptide and a maximal 80% inhibition of the enzyme activity. The galanin fragments (2–29) and (1–15) dose-dependently inhibited the forskolin-stimulated adenylate cyclase, while the fragments (3–29) and (10–29) were found inactive. These results indicate that the regulatory action of galanin in the central nervous system involves the coupling of galanin receptors to the inhibition of the adenylate cyclase system.

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Cited by (31)

Impairment of memory consolidation by galanin correlates with in vivo inhibition of both LTP and CREB phosphorylation
2009, Neurobiology of Learning and Memory
Changes in the state of CREB phosphorylation and in LTP in the hippocampus have been associated with learning and memory. Here we show that galanin, the neuropeptide released in the hippocampal formation from cholinergic and noradrenergic fibers, that has been shown to produce impairments in memory consolidation in the Morris water maze task inhibits both LTP and CREB phosphorylation in the rat hippocampus in vivo. While there are many transmitters regulating CREB phosphorylation none has been shown to suppress behaviorally-induced hippocampal CREB phosphorylation as potently as galanin. The in vivo inhibition of dentate gyrus-LTP and of CREB phosphorylation by the agonist occupancy of GalR1 and GalR2-type galanin receptors provides strong in vivo cellular and molecular correlates to galanin-induced learning deficits and designates galanin as a major regulator of the memory consolidation process.
Central galanin administration blocks consolidation of spatial learning
2003, Neurobiology of Learning and Memory
Galanin is a neuropeptide that inhibits the evoked release of several neurotransmitters, inhibits the activation of intracellular second messengers, and produces deficits in a variety of rodent learning and memory tasks. To evaluate the actions of galanin on encoding, consolidation, and storage/retrieval, galanin was acutely administered to Sprague–Dawley rats at time points before and after training trials in the Morris water maze. Intraventricular administration of galanin up to 3 h after subjects had completed daily training trials in the Morris water task impaired performance on the probe trial, indicating that galanin-blocked consolidation. Pretreatment with an adenylate cyclase activator, forskolin, prevented the deficits in distal cue learning produced by galanin. Di-deoxyforskolin, an inactive analog of forskolin, had no effect. These results provide the first evidence that galanin interferes with long-term memory consolidation processes. A potential mechanism by which galanin produces this impairment may involve the inhibition of adenylate cyclase activity, leading to inhibition of downstream molecular events that are necessary for consolidation of long-term memory.
Galanin inhibits acetylcholine release from rat cerebral cortex via a pertussis toxin-sensitive G(i) protein
1999, Neuropeptides
Galanin has been implicated in various physiological functions including memory, feeding and pain perception. Using rat cerebral cortical slices and synaptosome preparations incubated with [³H]choline in Kreb’s-Ringer solution, galanin was shown to inhibit both spontaneous and K⁺-stimulated [³H]ACh release in a concentration-related manner [EC₅₀= 35 nM]. The galanin-mediated inhibition on spontaneous and K⁺-stimulated [³H]ACh release was respectively regulated by pertussis toxin-sensitive G_αi3and G_αi1. These suggest that galanin is a negative modulator of cortical cholinergic function and most probably acting on presynaptic cholinergic terminals. Although galantide blocked the galanin-mediated inhibitory effect on [³H]ACh release, it mimicked galanin in blocking K⁺-stimulated [³H]ACh release, indicating that galantide may have a more complicated pharmacology than being a galanin receptor antagonist. In addition, we demonstrate that galanin and β-amyloid peptide_1–42synergistically attenuated K⁺-evoked [³H]ACh release from synaptosomes prepared from rat cerebral cortex. Since galanin is increased in Alzheimer’s disease brain, our results suggest that galanin may be involved in cholinergic dysfunctions that occur in Alzheimer’s disease.
Galaninergic signalling and adenylate cyclase
1998, Neuropeptides
Galanin is a hyperpolarizing, inhibitory neurotransmitter; its recognition by seven transmembrane spanning G-protein-coupled receptors leads to a change in accumulation of cAMP (3′5′-cyclic AMP). Different subtypes of galanin receptor and G-proteins could be manifested in the mode of inhibitory action of galanin receptor on the production of cAMP by adenylate cyclase. Galanin analogues, acting at the adenylate cyclase level as subtype-specific galanin antagonists, can selectively block the inhibitory effect of endogenous galanin and thereby have potential as therapeutic agents for several endocrine, neuroendocrine and neuronal disorders. In this review, the latest results in the field of interplay between galanin-initiated signal transduction and the cAMP pathway are summarized.
Chapter 5. Galanin Receptors: Recent Developments and Potential Use as Therapeutic Targets
1998, Annual Reports in Medicinal Chemistry
Galanin receptors: Involvement in feeding, pain, depression and Alzheimer's disease
1997, Life Sciences
Galanin, a neuroendocrine peptide with a multitude of functions, binds to and acts on specific G-protein coupled receptors. Only one galanin receptor subtype, GalR1, has been cloned so far, although pharmacological evidence suggests the presence of more than one galanin receptor subtype. These receptors mediate via different G_i/G_o-proteins the inhibition of adenylyl cyclase, opening of K⁺-channels and closure of Ca²⁺-channels. Galanin inhibits secretion of insulin, acetylcholine, serotonin and noradrenaline, while it stimulates prolactin and growth hormone release. Determination of structural components of galanin receptors required for binding of the peptide ligand as carried out recently will facilitate the screening and design of molecules specifically acting on galaninergic systems with therapeutic potential in Alzheimer's disease, feeding disorders, pain and depression.

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ArticleGalanin inhibits adenylate cyclase of rat brain membranes

Abstract

J. Biol. Chem.

Peptides

Neurosci. Lett.

Eur. J. Pharmacol.

Biochem. Biophys. Res. Commun.

J. Biol. Chem.

FEBS Lett.

Mechanism of galanin-inhibited insulin release: Occurrence of a pertussis toxin-sensitive inhibition of adenylate cyclase

Eur. J. Biochem.

Article
Galanin inhibits adenylate cyclase of rat brain membranes