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

The effect of Substance P infused intracerebrally via chronically implanted electrode-cannulae on self-stimulation induced from the same site was studied in rats. Substance P caused a significant depression of self-stimulation at 60 and 120 microgram/rat. Morphine infused into this site also caused significant depression of self-stimulation, but the doses were considerably lower than those of Substance P (5 and 10 microgram/rat). Pretreatment with naloxone, a narcotic antagonist, significantly antagonized the effects of Substance P on self-stimulation. It is proposed that Substance P modulates self-stimulation by the release of an endogenous morphine-like substance, but the possibility of a direct effect of Substance P was not ruled out.
 ...
PMID:Effect of substance P on medial forebrain bundle self-stimulation in rats following intracerebral administration. 59 92

The effect of substance P on the end-plate currents (EPC) and miniature EPC (MEPC) was studied in the "cut" sartorius muscle of the frog using voltage-clamp technique after acetylcholinesterase inhibition. Substance P in the concentration 5.10(-7)-1.10(-6) mol/l had no effect on the amplitude and time course of the single EPC and MEPC, but promoted significant prolongation of EPC decay during repetitive nerve stimulation (10/s), which indicated development of postsynaptic potentiation. Elevation of the substance P concentration to 5.10(-6) mol/l has led to the shortening of single EPS decay and more significant depression of the EPC amplitude in trains. This effect was connected with a decrease of the postsynaptic membrane sensitivity to acetylcholine, i. e. development of desensitization.
 ...
PMID:[The postsynaptic effects of substance P in the frog neuromuscular synapse]. 165 84

There are receptors on lymphocytes for substance P which are found both on small recirculating and on blast lymphocytes. The principal effect of substance P on lymphocytes appears to be a stimulating one, both in vitro and in vivo. The in vivo administration of substance P to sheep by acute infusion into cannulated afferent lymphatics of peripheral lymph nodes has been found to stimulate efferent lymph flow and the output into efferent lymph of both small recirculating and blast lymphocytes. We here report that substance P both enhances and prolongs the enhancement of the output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo. This output-stimulating effect appears to be specific to T4 (CD4) lymphocytes and is associated with a depressant effect on the output of T8 (CD8) and B lymphocytes. The output-stimulating effect on small T4 (CD4) lymphocytes is quite prolonged, lasting in excess of 96 h after a single 50 micrograms acute infusion. A brief post-infusion depression in T4 (CD4) lymphocyte output is associated with an equally brief, but marked, elevation in the output into efferent lymph of the arachidonic acid metabolite, thromboxane B2. The output-stimulating effect of substance P on blast T lymphocytes is confined to the T4 (CD4) blast lymphocytes. Substance P or a similar molecule may be of value when a specific T4 (CD4) lymphocyte output stimulant effect is desired. A single prior (6 days) acute infusion of substance P into a popliteal lymph node via its cannulated afferent lymphatic produced profound changes in the response to nodal drainage area immunization with killed S. muenchen bacteria. The latent period prior to increased antibody production was abolished, as was the standard post-immunization 'shutdown' period of decreased output of lymphocytes into efferent lymph. These changes were accompanied by a marked and progressive increase in antibody production. The findings reported here suggest substance P-induced long-term potentiation (LTP) of the immune response and raise the question of an involvement of substance P as a major mediator of immunological memory.
 ...
PMID:Substance P increases and prolongs increased output of T4 (CD4) lymphocytes from lymph nodes of sheep in vivo: is it a mediator of immunological memory? 170 49

The mammalian tachykinins, substance P and neurokinin A, and the non-mammalian tachykinin, physalaemin, were tested on functionally identified dorsal horn neurones in vivo. The experiments were done on cats which were anaesthetized with sodium pentobarbital or were anaemically decerebrated. Extracellular single-unit recordings were made in the lumbar spinal cord and the tachykinins were applied by iontophoresis. Each neurone was classified functionally as wide dynamic range, non-nociceptive, nociceptive specific or proprioceptive. The response to tachykinin application was determined for each neurone. Application of each of the tachykinins evoked a characteristic excitatory response which was delayed in onset, slow in developing and prolonged: physalaemin excited 99/131 neurones tested, neurokinin A excited 45/63 neurones and substance P excited 32/49 neurones. With two neurones physalaemin evoked a depression of the rate of firing, which may have been caused indirectly by excitation of a neighbouring neurone. Such depression was not elicited by either substance P or by neurokinin A. Physalaemin had a preferential excitatory effect on nociceptive neurones evoking excitation of 76/94 nociceptive neurones compared with 12/23 non-nociceptive neurones (chi 2 = 7.9, 1 d.f., P = 0.005). Substance P also caused a preferential excitation, with 30/40 nociceptive neurones being excited while all of the non-nociceptive neurones (n = 7) were unaffected (chi 2 = 11.5, 1 d.f., P = 0.0007). In contrast, neurokinin A failed to have a preferential effect; 32/46 nociceptive and 9/10 non-nociceptive neurones were excited (chi 2 = 1.0, 1 d.f., P = 0.40). Comparing the proportions of nociceptive neurones excited by the different tachykinins indicated that this type of neurone was not differently sensitive to any of the three peptides (chi 2 = 3.2, 2 d.f., P = 0.20). On the other hand, non-nociceptive neurones were preferentially excited by neurokinin A and physalaemin compared with substance P (chi 2 = 13.4, 2 d.f., P = 0.001). With regard to the endogenous tachykinins the results of this study may be interpreted in the following ways. The differential excitatory effect of substance P on nociceptive neurones supports the proposed role for this peptide in the transmission specifically of nociceptive inputs at the first afferent synapse. On the other hand, as neurokinin A excited non-nociceptive as well as nociceptive neurones, there may be a functional role for neurokinin A distinct from that of substance P.
 ...
PMID:Responses of functionally identified neurones in the dorsal horn of the cat spinal cord to substance P, neurokinin A and physalaemin. 171 88

Substance P (SP) and thyrotrophin-releasing hormone (TRH) are co-localized with serotonin (5-HT) in cells of the medullary raphe nuclei. In order to examine the factors that control development of multiple neurotransmitters within individual brain nuclei, we have grown presumptive raphe nuclei in organotypic tissue culture, an environment in which mammalian embryonic brain is easily accessible and manipulable. Tissue was obtained from E13 mice. A discrete midline segment of the rhombencephalon was dissected intact or was separated into 'rostral' (RR) and 'medullary' (MR) fragments. Tissue was explanted onto collagen coverslips and grown for up to two weeks in Maximow depression chambers. Tryptophan hydroxylase (TPH), the rate-limiting enzyme in 5-HT biosynthesis, was barely detectable at explantation. During the first week in culture, however, TPH activity increased 7-fold. After two weeks, TPH activity increased almost 2.5-fold above the one-week level. Immunocytochemical analysis of the cultures confirmed a widespread distribution of 5-HT-positive cells and fibers throughout the explant. SP, monitored by radioimmunoassay, was detected after two days in culture, and attained a level of 111.7 +/- 9.8 pg/culture after two weeks. TRH activity was similarly elevated after two weeks in vitro. Therefore, developmental increases in TPH, SP, and TRH occurred in culture, mimicking the condition in vivo. RR and MR fragments, when grown apart on separate coverslips, developed 1.57-2.26 times the TPH activity that developed in the undivided piece. Inclusion of 1 microM pargyline in the fragments restored TPH to control levels. The effect of pargyline was blocked by methiothepin, suggesting autoreceptor-mediated regulation.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Development of serotonin, substance P and thyrotrophin-releasing hormone in mouse medullary raphe grown in organotypic tissue culture: developmental regulation by serotonin. 246 25

Substance P, an 11 amino acid residue vasoactive neurotransmitter peptide, has been found on acute infusion (50 micrograms) into cannulated afferent lymphatics of popliteal lymph nodes of sheep to produce marked elevations in both efferent lymph flow and in the outputs of both blast and small recirculating lymphocytes into popliteal node efferent lymph (chronically cannulated). These elevations were characterized by a delay in the onset of major elevations, a marked prolongation of the elevations and a substantially greater stimulative effect on the output of blast lymphocytes. It is suggested that the number and types of substance P receptors on lymphocytes and in sheep peripheral lymph nodes may be responsible for these observations. Infusion of substance P, known for involvement in pain impulse transmission, was able to briefly overcome anaesthesia-induced depression in lymphocyte traffic. The substance P-induced alterations in lymph flow and lymphocyte traffic in vivo were demonstrated to be due to local rather than systemic effects of substance P.
 ...
PMID:Substance P increases lymphocyte traffic and lymph flow through peripheral lymph nodes of sheep. 247 54

The prevalence of severe dementia in the United States is about 1.3 million cases, of which at least 50 to 60% are of the Alzheimer type. Severe dementia of the Alzheimer type is found rarely in a clearly dominant pattern, although often one or more relatives are affected. Down's syndrome in adults is often associated with Alzheimer changes. The diagnosis is a clinicopathological one; there is a considerable error rate in the clinical diagnosis early in the course of the disease, especially in regard to dementia in depression. The differential diagnosis involves a great many disorders, including multi-infarct dementia, tumors, subdural hematomas, and others. Physiological aspects of Alzheimer's disease include a diffusely slow electroencephalogram, reduced cerebral blood flow, and particular patterns noted on positron emission tomographic scanning. The latter technique has also demonstrated that oxygen extraction is normal in Alzheimer's disease, thus excluding ischemia from possible pathogenetic factors. Morphological changes, that is, the presence of plaques and tangles, are widely distributed in neocortex, paleocortex, and many deep gray areas down through the pontine tegmentum, but largely exclude the basal ganglia, thalamus, and substantia nigra. Numerous plaques without neocortical tangles are found in many demented persons older than 75 years. A severe loss of large neocortical neurons is characteristic of the disease. The chemical nature of the paired helical filaments that make up the neurofibrillary tangle has not yet been ascertained. Neurons are markedly deficient in the basal forebrain nuclei, and this deficiency may account for the severe diminution of choline acetyltransferase and acetylcholine in the neocortex and paleocortex. Muscarinic cholinergic receptors are present in normal amounts. Norepinephrine is reduced in some cases, and somatostatin in most. Substance P is low in severe cases. The etiology of the disorder is unknown and the role of aluminum is disputed. Management of patients with Alzheimer's disease is difficult, and neuroleptics are to be used with great caution because of their side effects. Substrate therapy has not been effective; physostigmine improves memory but is not suitable for general use. Trophic factors, gangliosides, and aluminum chelation are being investigated for use in pharmacological intervention.
 ...
PMID:Senile dementia of the Alzheimer type. 613 75

Substance P injected into the lumbar subarachnoid space of rats depressed the tail-flick response to radiant heat in a dose-dependent way. The effective doses ranged from 0.1 microgram to 100 micrograms per rat (ED 50: 1.5 microgram/rat). The maximum of the effect was reached 20 min after intrathecal injection and the effect lasted for about 30 min. An antinociceptive effect was also observed after intrathecal injection of substance P 1 microgram to spinal rats. The depression of the tail-flick response produced by intrathecal administration of substance P was abolished by intrathecal (5 micrograms/rat) or i.p. (0.5 mg/kg) injections of naloxone.
 ...
PMID:Intrathecal substance P depresses the tail-flick response - antagonism by naloxone. 617 Aug 95

The effect of an injection of substance P into the subarachnoid space was studied on a motor and a sensory response elicited by supramaximal stimulation of the sural nerve in spinal rats. Substance P 10 micrograms depressed the reflex activation in the electromyogram recorded from the ipsilateral tibialis anterior muscle; the depression was significant 5 and 10 min after the injection. Substance P 10 micrograms reduced the activity in ascending axons of the spinal cord evoked by stimulation of afferent C fibres; the effect developed slowly, lasted longer than 60 min and was abolished by an i.v. injection of nalaoxone 0.2 mg/kg. Only half the number of ascending axons tested showed a depression by substance P, and the administration of a higher dose (50 micrograms) did not produce an effect in a greater number of axons. Substance P did not influence the activity evoked in ascending axons by stimulation of afferent A beta and A delta fibres. The depression by substance P of ascending nocieceptive activity was antagonized by an i.v. injection of naloxone 0.2 mg/kg. When naloxone 0.2 mg/ng i.v. was administered alone, it increased the activity in ascending axons activated by afferent C fibre stimulation. It is concluded that (i) substance P depresses spinal nociceptive activity without the intermediation of endorphinergic neurons, and (ii) naloxone antagonizes tonic inhibition of the spinal nociceptive system mediated by endogenous opioid peptides and, by facilitating excitatory transmission through disinhibition, neutralizes the depression produced by substance P.
 ...
PMID:Intrathecal substance P depresses spinal motor and sensory responses to stimulation of nociceptive afferents--antagonism by naloxone. 618 Mar 30

Substance P (0.5-5 microM) depressed the spike peak and after-hyperpolarization of action potentials of bullfrog sympathetic ganglion cells. It also depressed the after-hyperpolarization and prolonged the falling phase in Ca2+ spikes. The voltage-dependent K+ currents, both the delayed rectifier K+ current (Ik1) and the M current (Ik2), were suppressed by substance P, suggesting that the depression of the after-hyperpolarization may be due to suppression of these K+ currents.
 ...
PMID:Substance P inhibits the action potentials in bullfrog sympathetic ganglion cells. 619 94


1 2 3 4 5 6 Next >>