Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0011570 (depression)
 172,036 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The biological activity of two galanin (GAL) fragments, GAL-(1-16) and GAL-(17-29), was tested in vivo by using a spinal nociceptive flexor reflex model in the rat. Intrathecal (i.t.) GAL-(1-16) had a similar biphasic effect on the flexor reflex, with facilitation at lower doses and facilitation followed by depression at higher doses, as the full length peptide GAL-(1-29). GAL-(1-16) also effectively depressed the facilitation of the flexor reflex caused by i.t. substance P (SP) or C-fiber conditioning stimulation (CS) and potentiated the depressive effect of i.t. morphine on the reflex, both actions that have been reported earlier with GAL-(1-29). In contrast, i.t. GAL-(17-29), even at high doses, did not induce changes in the amplitude of the flexor reflex, nor did it interact with the effects of i.t. SP, morphine or C-fiber CS. It is concluded that the N-terminal portion of GAL-(1-29) is critical for the biological activity of the intact peptide in the dorsal horn of the rat spinal cord. The similarity between the effects of GAL-(1-16) and GAL-(1-29) indicates that they probably act on the same GAL receptor.
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PMID:The N-terminal 1-16, but not C-terminal 17-29, galanin fragment affects the flexor reflex in rats. 169 60

The effects of systemic PD134308 [0.1-3 mg/kg; an antagonist of the cholecystokinin (CCK) type B receptor], morphine, and intrathecal (i.t.) galanin (GAL) on the excitability of the spinal nociceptive flexor reflex and in the hot plate test were examined in rats. PD134308 caused a weak naloxone-reversible depression of the flexor reflex and a moderate antinociceptive effect in the hot plate test. However, PD134308 significantly potentiated the antinociceptive effect of morphine as well as its depressive effect on the flexor reflex. PD134308 and i.t. GAL synergistically depressed the flexor reflex, an effect that was reversed by naloxone. Finally, the magnitude and duration of the depression of the flexor reflex by morphine were synergistically increased by coadministering PD134308 and GAL i.t. The results demonstrated that a CCK antagonist directed to the central CCK type B receptor potentiates the analgesic effects of opioids and nonopioid drugs at the spinal level, thus supporting the notion that CCK in the central nervous system may be an endogenous, physiological opioid antagonist.
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PMID:PD134308, a selective antagonist of cholecystokinin type B receptor, enhances the analgesic effect of morphine and synergistically interacts with intrathecal galanin to depress spinal nociceptive reflexes. 169 90

The effect of intravenous (i.v.) PD134308, which is a CCK-B antagonist, morphine and intrathecal (i.t.) galanin (GAL) on the excitability of the spinal nociceptive flexor reflex and in the hot plate test was examined in rats. PD134308 (1 mg/kg, i.v.) caused a weak, naloxone-reversible depression of the flexor reflex and moderate antinociception in the hot plate test. PD134308 significantly potentiated the antinociceptive effect of morphone, as well as its depressive effect on the flexor reflex. PD134308 and i.t. GAL synergistically depressed the flexor reflex, which was reversed by naloxone. Finally, the magnitude and duration of the depression of the flexor reflex by morphine was synergistically increased by coadministering i.v. PD134308 and i.t. GAL. The results demonstrate that a CCK antagonist directed to the central CCK-B receptor potentiates the analgesic effects of opioid and non-opioid drugs at spinal level in the rat, thus supporting the notion that CCK in the CNS may be an endogenous, physiological opioid antagonist.
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PMID:Studies on the effect of systemic PD134308 (CAM 958) in spinal reflex and pain models with special reference to interaction with morphine and intrathecal galanin. 171 29

Recent immunohistochemical studies have shown the distribution of histaminergic neurons in the mammalian brain, which are concentrated in the tuberomammillary nucleus of the posterior hypothalamus and project efferent fibers to almost all parts of the brain from the olfactory bulb to the spinal cord. Histaminergic neurons co-express other neuroactive substances, such as gamma-aminobutyric acid, adenosine, substance P, galanin and Met-enkephalin-Arg-Phe. In addition, pharmacological studies have demonstrated the presence of presynaptic histamine H3-receptors (autoreceptor) in addition to H1- and H2-receptors. The specific agonist (alpha-methylhistamine) and antagonist (thioperamide) of H3-receptors were developed. Results from a number of studies indicate a variety of physiological roles of neuronal histamine such as thermoregulation, feeding behavior, sexual activity, sleep-wakefulness cycle, hormonal regulation and so on. Moreover, histaminergic drugs affect not only the emotional behavior, but also are effective to treat some patients of depression, Parkinson's disease, akathisia, motion sickness and so on. The central histaminergic neuron system is also affected by mental disorders and neuropsychopharmacological drugs. This review especially focused on these points and suggests that the central histaminergic neuron system may play an important role in the regulation of mental functions.
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PMID:[Recent advances in neuropsychopharmacology of the central histaminergic neuron system]. 192 57

Galanin is a peptide which stimulates feeding behavior in animals and is found within those basal forebrain cholinergic neurons which degenerate in Alzheimer's disease. Galanin was measured in cerebrospinal fluid (CSF) by radioimmunoassay. The nature of the immunoreactivity was characterized chromatographically as authentic galanin. CSF galanin levels were determined in subjects with Alzheimer's disease, involutional depression, anorexia nervosa and bulimia. No differences between any diagnostic group and age and sex-matched controls were found.
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PMID:Galanin immunoreactivity in human CSF: studies in eating disorders and Alzheimer's disease. 246 4

Galanin (GAL) was applied intrathecally (i.t.) at the lumbar level in decerebrate, spinalized, unanesthetized rats. GAL had no effect on the amplitude of the monosynaptic reflex over a wide concentration range, but at low concentrations if briefly facilitated the flexor reflex and at higher concentrations the facilitation was sometimes followed by a depression. GAL decreased the facilitatory effect of a conditioning stimulus train to C-fibers in the sural nerve. The depressive effect of GAL could be prevented by the i.t. coadministration of calcitonin gene-related peptide (CGRP), but not substance P (SP) and was not reversed by i.t. naloxone or bicuculline. The results illustrate the complex effect of GAL on the spinal cord, possibly exhibiting a biphasic effect. The observed effects on the flexor reflex are probably not due to changes in the excitability of motoneurons. Descending inhibitory pathways or local inhibitory non-GAL interneurons probably are not involved in the depressive effect of GAL. The possibility that the observed effects are related to primary sensory afferents containing not only GAL but also CGRP, and/or to local GAL neurons in the dorsal horn is discussed.
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PMID:The effects of intrathecal galanin and C-fiber stimulation on the flexor reflex in the rat. 247 74

The effect of intrathecal galanin (GAL) on the hamstring flexor reflex to sural nerve stimulation was compared in rats with intact and unilaterally sectioned sciatic nerves. GAL had a biphasic effect on the flexor reflex in rats with intact nerves, including facilitation, facilitation followed by depression and pure depression, in a dose-dependent manner. In axotomized rats, the depressive effect of GAL was significantly increased, occurring at lower drug concentrations. Furthermore, the degree of depression was significantly stronger with a more rapid onset after nerve section. It is concluded that along with an increase in GAL-like immunoreactivity in primary afferents, the inhibitory function of this neuropeptide is enhanced following axotomy. This functional change may be due to both pre- and postsynaptic mechanisms.
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PMID:The effect of intrathecal galanin on the flexor reflex in rat: increased depression after sciatic nerve section. 248 26

Galanin is a widely distributed 29/30 amino acid long neuropeptide with multiple biological effects. It inhibits glucose-induced insulin release, hippocampal acetylcholine release, hippocampal glutamate but not GABA release, and it lowers spinal excitability and firing of locus coeruleus neurons. It stimulates food (fat) intake and growth hormone release upon hypothalamic or i.c.v. injection. Galanin actions are mediated via high affinity Gi/G0 protein-coupled receptors--involving effector systems such as K(+)-, Ca(2+)-channels and adenylate cyclase. Galanin receptor agonists are thought to have therapeutic application in treatment of chronic pain and prevention of ischemic damage; galanin receptor antagonists have therapeutic potential in the treatment of Alzheimer's disease, depression, and feeding disorders.
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PMID:Galanin--a neuroendocrine peptide. 769 57

We have examined the effects of intrathecal (i.t.) galanin message-associated peptide (GMAP), the C-terminal flanking peptide in the galanin (GAL) precursor protein, which is produced in equimolar quantities with galanin and which is upregulated upon axotomy, on the spinal nociceptive flexor reflex in decerebrate, spinalized, unanesthetized rats. I.t. GMAP elicited a moderate facilitation of the flexor reflex. No depression of baseline flexor reflex was observed with any dose of GMAP. The facilitation of the flexor reflex induced by conditioning stimulation (CS) of cutaneous C-afferents was dose-dependently blocked by GMAP. The reflex facilitatory effect of exogenously applied substance P (SP), one of the endogenous modulators of reflex hyperexicitability following C-fiber CS, was only blocked by GMAP at a relatively high dose. I.t. GMAP did not antagonize the reflex facilitatory effect of vasoactive intestinal peptide and did not potentiate the reflex depressive effect of i.t. morphine or clonidine. Finally, 1 micrograms i.t. GMAP did not influence spinal cord blood flow whereas 10 micrograms GMAP induced a transient decrease in spinal cord blood flow in some experiments. The ability of GMAP to block the increase in spinal cord excitability following repetitive C-fiber stimulation may be through a presynaptic action. Although some of the effects of GMAP were similar to galanin, distinct differences were found, particularly in interaction with other excitatory and inhibitory agents. It is possible that GMAP exerts its action in the spinal cord through its own specific receptor. GMAP may act similarly to GAL in some, but not all pharmacological functions.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effects of intrathecal galanin message-associated peptide (GMAP) on the flexor reflex in rats. 857 Aug 56

Galanin (GAL)-immunoreactive axon terminals on motor endplates of the esophageal striated muscles were demonstrated in mice, guinea-pigs and rats. The GAL-terminals innervated 33% of AChE-reactive motor endplates in mice and 6% of those in guinea-pigs. Double immunostaining revealed that separate GAL- and CGRP-positive terminals were localized within the same motor endplates in mice and rats. The GAL and CGRP terminals had different morphologies. No CGRP-immunoreactivity was found on motor endplates of the guinea-pig esophagus. Double immunostaining in rats showed that 68% of motor endplates with CGRP-nerve terminals were also supplied by GAL-nerve terminals, suggesting that the majority of esophageal striated muscles receive a dual innervation of GAL-and CGRP/ACh-containing terminals. By immuno-electronmicroscopy in the rat esophagus. GAL-immunoreaction was found in a small type of nerve terminals that possessed many large cored vesicles (90-130 nm) with intense immunoreaction. Larger GAL-negative nerve terminals with a cluster of small clear vesicle (40-50 nm), which seemed to be ACh-containing nerve terminals, were adjacent to a depression or slight protrusion of the sarcolemma and well-developed folds in the muscle fibers. At the motor endplates, the GAL-positive terminals made a synaptic contact via basement membrane with the sarcolemma of the muscle fibers, which was characterized by post-synaptic intense electron density. In most of all situations, in which the GAL-positive terminals and GAL-negative or -positive terminals were adjacent to each other and were also apposed to the striated muscles, the terminals were separated by attenuated sheet- or tongue-like cytoplasmic processes that appeared to originate from Schwann cells. Thus, the GAL-nerve terminals seem to provide a direct innervation of the striated muscle fibers rather than innervating the ACh-containing motor nerve terminals adjacent to the GAL-terminals.
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PMID:Galanin-containing nerve terminals that are involved in a dual innervation of the striated muscles of the rat esophagus. 889 24


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