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)

Somatostatin (somatotropin release-inhibiting factor, SRIF) was originally discovered (1) during the purification of growth hormone-releasing factor from rat hypothalamus and was subsequently isolated and characterized (2) in 1972 from ovine hypothalamus. Since its initial characterization, SRIF has been shown to fulfill criteria for a neurotransmitter and to directly modulate neuronal activity as well as acting as an inhibitory factor regulating endocrine and exocrine secretion. Alterations in cerebrospinal fluid (CSF) concentrations of SRIF have been reported in several diseases exhibiting prominent cognitive dysfunction, including Alzheimer's disease (AD), major depression, Huntington's chorea, multiple sclerosis, schizophrenia and Parkinson's disease, while evidence for regional brain tissue concentration deficits in SRIF are more specific for AD. This mini-review will focus on the studies reporting alterations in CSF and postmortem tissue concentrations of SRIF in AD and depression.
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PMID:Somatostatin in Alzheimer's disease and depression. 135 21

The facilitatory effect of intrathecal (i.t.) morphine on the excitability of the nociceptive flexor reflex was examined in decerebrate, spinalized, unanesthetized rats with intact or sectioned sciatic nerves. Low doses of i.t. morphine (10 ng in rats with intact nerves and 10 or 100 ng in rats with sectioned nerves) facilitated the flexor reflex. Higher doses of morphine caused facilitation followed by reflex depression. Facilitation of the flexor reflex induced by 10 or 100 ng morphine was prevented by i.t. naloxone (1 microgram). In rats with intact sciatic nerves the facilitation was partially antagonized by the tachykinin antagonist spantide II (D-NicLys1,3-Pal3,D-Cl2Phe5,Asn6,D-Trp7,9,Nle 11)-substance P (SP), indicating that the reflex facilitation evoked by low doses of morphine may be due to the release of SP and perhaps other neuropeptides. In axotomized animals, 14-20 days after unilateral sciatic nerve section, spantide II failed to antagonize morphine-induced facilitation, suggesting that SP or other tachykinins, no longer played a role in this effect. In contrast, the vasoactive intestinal peptide (VIP) antagonist (N-Ac-Tyr1,D-Phe2)-GRF (1-29)-NH2 blocked morphine-induced reflex facilitation in axotomized rats, but not in rats with intact nerves. The present study provides evidence that low doses of morphine may induce the release of excitatory neuropeptides, thereby facilitating spinal nociceptive transmission. The identity of the neuropeptides depends on whether or not peripheral axons are intact, tachykinins in rats with intact nerves and VIP in axotomized rats.
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PMID:Low-dose intrathecal morphine facilitates the spinal flexor reflex by releasing different neuropeptides in rats with intact and sectioned peripheral nerves. 171 3

Dietary nitrate significantly inhibits the growth of male and female rats. To test the possibility that the growth hormone-releasing factor (GRF) content in hypothalamic tissue is deranged under these conditions, male and female rats were fed a diet containing 3% KNO3 for 6 weeks, compared to a normal diet (4 X 5 animals). The food intake of rats fed nitrate was reduced significantly (23 and 28% resp.). Weight gain was also decreased by 35 and 41% in male and female rats. The mean Sm-C/IGF-I concentration was 1.61 and 1.03 rU/ml in male and female control rats, whereas the concentrations in nitrate-exposed rats were 0.92 and 0.64, respectively (P less than 0.01). The GRF content of hypothalamic tissue also decreased significantly from 407 and 533 ng/g protein in controls to 174 and 229 in treated male and female rats. Nitrate exposure is characterized by hypothyroidism, food intake depression, low Sm-C/IGF-I concentrations in plasma and a decreased hypothalamic GRF content. Independent of the peripheral changes, the content of Sm-C/IGF-I in the brain remains constant. The results of the study demonstrate that thyroid hormone deficiency leads to an inhibition of GH axis already at the hypothalamic level.
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PMID:Nitrate-induced hypothyroidism is associated with a reduced concentration of growth hormone-releasing factor in hypothalamic tissue of rats. 186 11

1. Comparative studies on the effects of vasoactive intestinal polypeptide (VIP), commercially available VIP antiserum or VIP antagonists [Ac-Tyr1, D-Phe2]-GRF(1-29)-NH2 and [4-Cl-D-Phe6, Leu17]-VIP on excitatory neuroeffector transmission in the dog and cat trachea were performed with microelectrode, double sucrose-gap, and tension recording methods. 2. VIP (10(-11)-10(-9) M) had no effect on the resting membrane potential or on the input resistance of the smooth muscle cells of dog and cat trachea. However, with increased concentrations (greater than 10(-8) M) VIP hyperpolarized the membrane and decreased the input resistance of the membrane in both tissues. 3. VIP (10(-10)-10(-7) M) dose-dependently reduced the amplitude of the contractions evoked through the nervous structure excited by field stimulation in the combined presence of indomethacin (10(-5) M) and guanethidine (10(-6) M) in the dog, and in the presence of guanethidine (10(-6) M) in cat trachea. In parallel with actions on twitch contractions, VIP (10(-11)-10(-7) M) reduced the amplitude of the excitatory junction potentials (EJPs) evoked through the nervous structure excited by single pulse field stimulation in both tissues. 4. VIP (10(-9) M) had no effect on the post-junctional response of smooth muscle cells to exogenous acetylcholine (ACh) (10(-9)-10(-5) M). 5. During repetitive field stimulation at the stimulus frequency of 0.033-0.1 Hz, the amplitude of the EJPs was gradually reduced, and VIP (10(-9) M) enhanced this depression phenomenon in the dog and cat trachea. 6. EJPs also showed summation when repetitive field stimulation was applied at high frequency (20 Hz) in the dog trachea. The slope of the relationship between the relative amplitude of the EJP and number of stimuli at 20 Hz was 2.2 +/- 0.4 mV/stimulation (n = 4) in the dog trachea. However, in the cat trachea, summation of EJPs was not prominent, giving a mean slope of 0.6 +/- 0.2 mV/stimulation (n = 6) measured by the microelectrode method. VIP (10(-9) M) shifted downward the relationship between the relative amplitude of the EJP and the number of stimuli at 20 Hz in both tissues. 7. Overnight incubation with VIP antiserum (10(-6) g/ml) had little effect on the depression of the EJP in the dog and cat trachea, or the summation of the EJP observed in the dog trachea.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Modulation of cholinergic neurotransmission by the peptide VIP, VIP antiserum and VIP antagonists in dog and cat trachea. 217 20

To explore and to compare hypothalamic-pituitary-somatotropic (HPS), hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenocortical (HPA) axis function in depression, 30 subjects (15 patients with a major depressive episode and individually matched controls) received 50 micrograms growth hormone-releasing hormone-44 amide at 9:00, 200 micrograms thyrotropin-releasing hormone (TRH) at 9:00 and 100 micrograms human corticotropin-releasing hormone (CRH) at 18:00 on consecutive days as an i.v. bolus dose. Compared with controls, depressed patients showed blunted growth hormone (GH) responses to GHRH, decreased TRH-induced thyrotropin (TSH) release and reduced corticotropin (ACTH) but normal cortisol secretion following CRH. ACTH secretion following CRH and TRH-induced TSH release were positively correlated across depressed patients and controls but no significant correlations between GH responses to GHRH and TRH-induced TSH release or ACTH and cortisol secretion following CRH administration were demonstrated. Our findings suggest that altered HPT and HPA axis function associated with depression are triggered by factors that are at least partly different from those that cause HPS system dysfunction. We conclude that the pathophysiological process resulting in aberrant neuroendocrine secretory dynamics associated with depression may primarily occur at a suprapituitary site, and that HPS, HPT and HPA axis dysfunction may be precipitated by complex central and peripheral regulatory mechanisms involving largely independent factors.
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PMID:Endocrine responses to growth hormone-releasing hormone, thyrotropin-releasing hormone and corticotropin-releasing hormone in depression. 254 70

The authors administered the growth hormone-releasing factor (GRF) stimulation test to 19 patients with major depression and 19 age- and sex-matched control subjects to test the hypothesis that a blunted growth hormone (GH) response to clonidine reflects a central alpha 2-adrenergic receptor subsensitivity in depression. GH response to GRF was significantly higher in patients with depression than in control subjects. This group difference was mainly attributable to three of the 19 depressed patients who exhibited markedly high GH responses to GRF. These results suggest that the blunted GH response to clonidine seen in patients with depression is not due to a pituitary defect in GH secretion.
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PMID:Growth hormone-releasing factor stimulation test in depression. 282 32

A blunted growth hormone (GH) response to clonidine and other pharmacologic stimuli has been reported in patients with depression. This blunted growth hormone response to clonidine has led to the speculation that there is a central alpha-2 adrenergic receptor subsensitivity in depression. This hypothesis is based on the assumption that the pituitary somatotroph response to growth hormone-releasing factor (GHRF) is not altered in depression. In the present preliminary study, the somatotroph response to GHRF in depressed patients and normal controls has been evaluated in four depressed patients and four age- and sex-matched controls. The GH response to GRF is highly variable both in normal individuals and in the depressed patients studied. Larger numbers of patients and controls must be studied before any definitive conclusions can be drawn about GH responses to GRF in depressed patients.
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PMID:Growth hormone response to growth hormone-releasing factor in depression. 285 37

To explore the GHRH-GH-somatomedin axis integrity in major depressive disorder, 11 drug-free patients and normal subjects matched for age, sex, ovarian status, and body weight received 1 microgram/kg synthetic human GHRH-44 amide as an iv bolus dose. Compared to the normal subjects, the depressed patients had reduced mean basal serum GH levels [2.2 +/- 0.5 (+/- SE) vs. 1.1 +/- 0.2 ng/mL (micrograms/L); P less than 0.05] and a significant attenuation of the net GH response to GHRH [1346 +/- 499 vs. 217 +/- 46 ng.min/mL (micrograms.min/L); P less than 0.01]. The blunted GH responses occurred in the face of significantly increased plasma somatomedin C (Sm-C) levels [1.1 +/- 0.2 vs. 0.6 +/- 0.1 U/mL; P less than 0.05]. The magnitude of GH responses to GHRH did not differ between men and women and was not significantly correlated with age, body weight, baseline serum GH levels, or plasma Sm-C levels in either individual groups or both groups combined. The increased plasma Sm-C levels in the depressed patients could have resulted from diurnal hypersecretion of GH, and the diminished GH responses to GHRH may reflect normal Sm-C-mediated feedback at the level of the pituitary. The presumed GH hypersecretion may be due to decreased hypothalamic somatostatin release and/or hyperactivity of GHRH-containing neurons. Thus, the pathological process resulting in abnormal GH secretory patterns associated with depression may occur primarily at a suprapituitary site.
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PMID:Growth hormone (GH) response to GH-releasing hormone in depression. 311 57

The effects of iontophoretically applied human pancreatic growth hormone-releasing factor (hpGRF), peptide histidine isoleucine (PHI-27), and somatostatin (SS) on the extracellular activity of single cells in the hypothalamus, thalamus, and cortex of the rat brain were studied in urethane-anesthetized, male rats. Neurons with membrane sensitivity to hpGRF, PHI-27, and SS were present in each brain region. Although neurons excited by these peptides were encountered in thalamus and hypothalamus, depression of neuronal firing was the predominant response observed. Overall, the neurons responding to hpGRF also possessed membrane sensitivity to PHI-27, whereas, the hpGRF sensitive neurons appeared to be more divided as to their ability to respond to SS. The results clearly demonstrate that hpGRF and PHI-27 are capable of affecting the membrane excitability of neurons in several brain regions. The distribution of neurons sensitive to hpGRF suggests that hypothalamic GRF, in addition to its well documented role in the regulation of pituitary growth hormone secretion, may subserve other physiological events in the rat central nervous system as a neurotransmitter and/or neuromodulator.
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PMID:Sensitivity of rat forebrain neurons to growth hormone-releasing hormone. 393 50

The effect of a subcutaneous bolus injection of 2 micrograms magnitude of Ac,Tyr1,D-Phe2-GRF(1-29) amide, a specific VIP antagonist (VIP-A), on the hypothalamo-pituitary-adrenocortical (HPA) axis were investigated in both normal and ether- or cold-stressed rats. Blood concentrations of ACTH, aldosterone (ALDO) and corticosterone (B) were measured by specific RIA 1, 2 or 4 h after VIP-A injection. VIP-A administration to normal rats strikingly lowered the plasma concentration of ALDO, without significantly affecting those of ACTH and B. Ether and cold stresses notably raised the blood levels of ACTH, ALDO and B, and these rises lasted unchanged until 4 h. VIP-A did not affect the response of HPA axis to ether stress, but provoked a marked depression of that to cold stress. In light of these findings the following conclusions can be drawn: (i) endogenous VIP does not regulate HPA-axis function under basal conditions, but it plays a pivotal role in the mechanisms involved in the activation of HPA axis induced by cold exposure; and (ii) endogenous VIP exerts a tonic stimulatory action on ALDO secretion, probably by acting directly on the adrenal zona glomerulosa.
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PMID:Evidence that endogenous vasoactive intestinal peptide (VIP) is involved in the regulation of rat pituitary-adrenocortical function: in vivo studies with a VIP antagonist. 786 61


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