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)

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

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.
 ...
PMID:The effects of intrathecal galanin and C-fiber stimulation on the flexor reflex in the rat. 247 74

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

To determine whether anti-allergic drugs can inhibit autonomic neurotransmission of airway smooth muscle, we studied the effect of sodium cromoglycate (SCG, Intal) and related anti-allergic drugs on electrically induced neurogenic contractions of isolated guinea pig bronchial muscle. Electrical field stimulation (8 Hz, 0.5 msec, 30 V) evoked a biphasic contraction of bronchial muscle, consisting of an initial phasic component followed by a sustained one which was mediated by cholinergic and non-cholinergic nerve stimulations, respectively. Sodium cromoglycate, tranilast, ketotifen, and azelastine at concentrations higher than 10(-6) M caused a concentration-dependent inhibition in the height of the non-cholinergically mediated contractions. The cholinergically mediated contractions were also inhibited by tranilast, ketotifen, and azelastine but not by SCG. Submaximal contractions of bronchial muscle evoked by exogenous substance P (2 X 10(-7) M) were less potently inhibited by these drugs than those by exogenous acetylcholine (2 X 10(-6) M). These results indicate that in isolated guinea pig bronchial muscle, anti-allergic drugs may inhibit non-cholinergic neurotransmission mainly by prejunctional reduction of the transmitter release and partly by postjunctional depression of the response.
 ...
PMID:Inhibitory effect of anti-allergic drugs on cholinergic and non-cholinergic neurotransmissions of guinea pig bronchial muscle in vitro. 247 61

Chronically implanted rats were injected either with somatostatin (SST) lumbar intrathecally (i.t.) (100 micrograms, n = 5), into the fourth ventricle (3 micrograms, n = 5; 10 micrograms, n = 6; 30 micrograms, n = 5) or into the lateral ventricle (10 micrograms, n = 6; 30 micrograms, n = 6), or received an injection of the substance P (SP) analogue, [D-Pro2, D-Trp7,9]SP into the fourth ventricle (0.3 micrograms, n = 2; 1 micrograms, n = 4; 3 micrograms, n = 4; 10 micrograms, n = 1) or lateral ventricle (3 micrograms, n = 3). A dose-dependent EEG depressant effect was observed following fourth and lateral ventricular injections of SST and of the SP analogue. Acute death due to respiratory depression was observed following i.t. and fourth ventricular injection of SST, and fourth ventricular injection of the SP analogue. Prominent motor behavior (barrel rotation, circling, cranial stereotypies) was observed, without signs of EEG seizure activity, following intraventricular injection of both drugs. Present findings indicate neurotoxic effects of SST and SP analogue at the cerebral level.
 ...
PMID:Electroencephalographic and behavioral assessment of intracerebroventricular somatostatin and a substance P analogue. 247 57

The effects of a new analogue of substance P (SP-A) and its interaction with substance P (SP) were studied in vitro isolated preparations from rabbit renal arteries and rat renal and pulmonary arteries. SP-A in did not affect the resting tone and the contractions of the rabbit renal arteries, evoked by field electrical stimulation (FES) but dose-dependently (10(-10)M - 5 X 10(-8)M) antagonized the inhibitory effects of SP on the FES-provoked contractions, the antagonism being of a non-competitive type. In the rat renal arteries SP had two different effects--depression of the FES-evoked contractions, and increase of the resting tone. SP-A did not exert per se effects on the tone and on the electrically-provoked contractions in these arteries. SP-A non-competitively antagonized both actions of SP in the same vessels. In rat pulmonary arteries SP increased the resting tone, whereas SP-A did not affect the resting tone and the FES-induced contractions. SP-A non-competitively antagonized the tone-increasing action of SP. The new analogue of SP may be useful in studying the mechanism of action of SP and its role in physiological and pathological reactions.
 ...
PMID:A new analogue of substance P with antagonistic properties in renal and pulmonary arteries. 248 80

Canine and human coronary arteries were studied in organ baths to compare the responses to acetylcholine and serotonin in the two species. The human coronary rings were isolated from seven patients without cardiac disease (mean age 15 years, range 7-20). In one set of experiments canine and human preparations were incubated with phentolamine, propranolol and ketanserin (all at 1 mumol.litre-1 concentration) and precontracted with prostaglandin F2 alpha (PGF2 alpha 1-2 mumol.litre-1). Acetylcholine (0.1-10 mumol.litre-1) and serotonin (0.1-100 mumol.litre-1) relaxed canine preparations dose dependently, the maximum responses (expressed as % of depression of PGF2 alpha response) being 84 (SEM 6)% (n = 9) and 51(5)% (n = 6) respectively. In the same experimental conditions, acetylcholine and serotonin failed to relax the human coronary rings (n = 11) while substance P and bradykinin induced relaxations of 72(4)% (n = 11) and 66(7)% (n = 11) of PGF2 alpha response respectively. In another set of experiments, dose-contraction curves were constructed for acetylcholine or serotonin (in presence of phentolamine and propranolol). On human rings with endothelium, methylene blue (10 mumol.litre-1), a non-specific inhibitor of endothelium derived relaxing factor (EDRF), potentiated these dose-contraction curves: markedly for serotonin, the EC50 decreasing from 1.2(0.2) to 0.22(0.08) mumol.litre-1 (n = 11, p less than 0.01) with a significant increase in the maximal response); and slightly for acetylcholine, EC50 decreasing from 0.84(0.11) to 0.40(0.13) mumol.litre-1 (n = 10, p less than 0.05) without significant change in the maximal response.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Comparison of responses to acetylcholine and serotonin on isolated canine and human coronary arteries. 248 33

Male Sprague-Dawley rats weighing 280-300g were used. To achieve the long-term administration of drugs into the epidural space without anesthesia, a new method of epidural tubing was used. A polyethylene catheter was inserted for 1.5cm into the epidural space through a slit made in the ligamentum flavum of L2-L3 intervertebral space. When 0.1ml of contrast media was injected through this catheter, the media spread from lumbar to upper thoracic vertebral region, as demonstrated with X-ray pictures. The rats with an epidural catheter were injected with 0.1ml of 2% capsaicin solution into the epidural space once a day for 4 days. Control rats were administered with the same volume of capsaicin-free vehicle. The depression of substance P at the dorsal horn (C6, Th7, L1) was investigated by the indirect immunofluorescence technique of Coons. One day after the end of capsaicin administration the depression of substance P was remarkable at laminae I-II in dorsal horn. But 14 days after the end of administration, substance P content at laminae I-II returned to the level of control rats. It was concluded that the depression of substance P by consecutive epidural capsaicin is reversible.
 ...
PMID:[Effect of epidural capsaicin on substance P in the dorsal horn in adult rats using epidural tubing]. 248 72

The hypothesis that acetylcholine, substance P, and LHRH suppress M-current by activating phospholipase C was tested. Each agonist caused turnover of phosphoinositide, as measured by release of inositol phosphates, and a modest transient rise in intracellular free Ca2+ ([ Ca2+]i), as determined with fura-2. Active phorbol esters depressed M-current only 50% and did not prevent further suppression by LHRH. M-current, its control by agonists, and its depression by phorbol esters were not affected by adding inositol trisphosphate or Ca2+ buffers with high or low Ca2+ to the whole-cell, voltage-clamp pipette. We conclude that phospholipase C activation does occur but does not mediate the suppression of M-current by agonists. Caffeine produced large [Ca2+]i transients and acted as an agonist to suppress M-current.
 ...
PMID:Agonists that suppress M-current elicit phosphoinositide turnover and Ca2+ transients, but these events do not explain M-current suppression. 248 99

Intracellular recordings were made from neurons in the submucous plexus of the guinea-pig caecum. Muscarinic agonists (acetylcholine, bethanechol and muscarine) depolarized about 70%, and hyperpolarized about 30% of the submucous plexus neurons. Low concentrations of pirenzepine reversibly antagonized both responses. The measured dissociation constants (KD) of 10-30 nM for the depolarizations and 1-3 nM for the hyperpolarizations suggest that each response was mediated by muscarinic M1 cholinoceptors. The muscarinic depolarization and hyperpolarization were associated with a decreased and an increased conductance, respectively, and the reversal potential for the muscarinic responses varied as the potassium concentration varied, always being around the potassium equilibrium potential. In cells depolarized by muscarinic agonists these agents appeared to decrease a potassium conductance that could also be inactivated by substance P. In approximately 30% of the submucous neurons, the slow inhibitory postsynaptic potential, elicited in response to single or repetitive focal stimuli (1-10 pulses at 20-40 Hz), appeared to consist of a large component which was sensitive to the blocking action of idazoxan (100-300 nM) and a small component which was idazoxan-insensitive. The latter (muscarinic slow inhibitory postsynaptic potential) was completely abolished by pirenzepine. The concentrations of pirenzepine which caused a 50% depression ranged from 5 to 20 nM. The muscarinic slow inhibitory postsynaptic potential was increased in amplitude and duration by physostigmine (100-300 nM). The muscarinic slow inhibitory postsynaptic potential was accompanied by a decrease in membrane input resistance, and was reversed in polarity near the potassium equilibrium potential. When muscarine induced a hyperpolarization and/or focal stimulation elicited a muscarinic slow inhibitory postsynaptic potential in the presence of idazoxan (100-300 nM), the intracellular injection of guanosine 5'-O-(3-thiotriphosphate) produced a progressive membrane hyperpolarization during which the muscarinic hyperpolarizing responses were attenuated. It is concluded that the muscarine-induced reduction in potassium conductance is mediated through a muscarinic M1 receptor which has a relatively low affinity for pirenzepine. The muscarine-induced increase in potassium conductance is probably produced by the association of a guanine nucleotide-binding regulatory protein with another muscarinic M1 receptor that has a relatively high affinity for pirenzepine.
 ...
PMID:Muscarinic excitation and inhibition of neurons in the submucous plexus of the guinea-pig caecum. 257 Mar 77


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>