Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Immunological aspects of neurosecretory peptides are relevant to antibody generation, labelling of peptides for radioimmunoassays and in particular the metabolism of neuropeptides. Antibodies were generally produced by adsorption or polymerization (using different approaches and various coupling agents) of peptides with intrinsic antigenic molecules preceding their administration to recepient animals (rats, guinea pigs, rabbits and sheep) with adjuvants. Antibodies were also obtained by injecting peptides alone with or without adjuvants. However, independent of the recipient species, the highest specific or nonspecific antibody titers were obtained by the former method. Up to now, only 3H-peptides or 125I-peptides or derivatives were used as tracers in RIAs. Highest sensitivities were generally obtained when using 125I-peptides. However, 125I-peptides may be adsorbed ("false titers") to some antiserum with sufficient specificity in terms of displacement by structural analogues of the peptide but with a loss of sensitivity. Finally, large molecular forms, cross-reacting with the antibodies prepared with different methods and peptidasic activities must be taken into account. These topics are presented with data on LHRH, TRH and substance P derived from our experiments and from those of other investigators.
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PMID:[Radioimmunological aspects of neuropeptides]. 9 97

A large-scale purification of monkey brain arylamidase was carried out. Amino acid analyses indicate that the enzyme is rich in acidic amino acids and is poor in cystine. The amino terminal residue was determined to be alanine by dansylation. The enzyme was activated by sulfhydryl compounds. Dithiothreitol was more effective than beta-mercaptoethanol. Bestatin competitively inhibited the enzyme activity and the Ki value was calculated to be 2.5 x 10(-7) M, which was of the same order as that of puromycin. The inhibitions by puromycin and bestatin were reversible. The enzyme hydrolyzed di-, tri-, and oligopeptides including physiologically active peptides. Of physiologically active peptides, enkephalins and Met-Lys-bradykinin, which possess a neutral amino acid at the N-terminal position, were more rapidly hydrolyzed by the enzyme. Peptides such as LH-RH and TRH, which possess a pyrrolidonecarboxylyl group at the N-terminal position, and substance P and bradykinin, which possess a proline residue adjacent to the N-terminal residue, were not hydrolyzed by the enzyme. The Km values for various peptides indicate that the enzyme has higher affinity for oligopeptides than di- and tripeptides. The aminopeptidase activity of the enzyme was also competitively inhibited by puromycin and bestatin. Analyses of the hydrolysis products of various peptides by the dansylation method indicate that the enzyme has both kinin-converting activity and angiotensinase activity.
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PMID:Monkey brain arylamidase. II. Further characterization and studies on mode of hydrolysis of physiologically active peptides. 10 79

The effects of bombesin and other unrelated oligopeptides on hormonal changes induced by stress were studied in conscious adult male rats. Restraint in the cold for 1 h increased plasma corticosterone and PRL levels and decreased GH values but had no effect on LH levels. Bombesin (5 microgram), given intracerebroventricularly (ivt) before stress, inhibited the PRL rise without affecting corticosterone, GH, or LH response. A complete blockade of PRL rise was observed with doses of bombesin ranging from 5 microgram to 100 ng ivt, regardless of the duration (15, 30, 45, or 60 min) or the nature (cold exposure or restraint at room temperature) of the stressor agents. Bombesin was 10(3) more potent as a PRL inhibitor when given ivt than when given iv, and its ivt effect was not reversed by naloxone (1 or 10 mg/kg). Among other unrelated peptides tested (beta-endorphin, neurotensin, substance P, and TRH; 5 microgram ivt), only neurotensin decreased plasma PRL levels in rats subjected to restraint in the cold for 1 h. These results show that in conscious male rats, centrally administered bombesin has a very potent and long acting inhibitory effect on PRL release induced by acute stress. Since a bombesin-like peptide has been found in rat brain, its physiological role in PRL regulation remains to be elucidated.
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PMID:Effects of neuropeptides on adenohypophyseal hormone response to acute stress in male rats. 10 88

Intraventricular injections of substance P, TRH and somatostatin were administered to rats rendered hypokinetic by bilateral microinjections of 6-hydroxydopamine into the anterolateral hypothalamus, Only substance P in a dose of 0.30 micrigrams/rat significantly increased motor activity as determined by photocell counts in a 5 min test session immediately after administration of the peptide. Behavioral observations indicated that grooming and not locomotion was mainly responsible for the greater activity scores. None of the three peptides at the doses examined potentiated or reduced the increased activity induced by 1 mg/kg apomorphine. Stereotyped behavior was also not affected by previous injections of substance P and somatostatin but was enhanced in animals which had received 5 micrograms/rat TRH 30 min prior to apomorphine.
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PMID:Effect of brain peptides on hypokinesia produced by anterolateral hypothalamic 6-OHDA lesions in rats. 11 89

Administered by either intravenous (i.v.) or intracisternal (i.cis.) injections, MK-771 and TRH induced a dose-related increase in EMG activity recorded from the flexor ulnaris muscle in pentobarbital-anesthetized rats. By the i.v. route, MK-771 was 6 times more potent than TRH and with i.cis. administration MK-771 was some 30 times more active than TRH. At equieffective doses of the two peptides, MK-771 exhibited a greater (approximately 3 fold) duration of action than TRH. In unanesthetized, spinally transected rats MK-771 was also more potent than TRH in eliciting EMG activity recorded from the biceps femoris muscle. Substance P, administered by the i.cis route failed to induce EMG activity. Intracisternally administered neurotensin, which did not affect EMG activity by itself, antagonized the actions of MK-771 while somatostatin was inactive in this regard. Neurotensin did not affect the EMG activity induced by physostigmine. While these studies do not delineate the mechanism whereby TRH and MK-771 induce EMG activity, it appears reasonable to suggest that TRH and related peptides, such as MK-771, may have some influence in functional disorders of human muscle.
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PMID:MK-771-induced electromyographic (EMG) activity in the rat: comparison with thyrotropin releasing hormone (TRH) and antagonism by neurotensin. 11 37

Neuronal compartments can be separated by differential spinning or by centrifugation on continuous or discontinuous density gradients. Application of these fractionation techniques to brain structures containing neurosecretory neurons shows that LHRH, somatostatin and a non dopamine prolactin inhibiting factor (PIF) are exclusively recovered from synaptosomal fractions. This indicates that biologically and/or immunologically reactive forms of these hormones are almost entirely concentrated in nerve-endings of neurosecretory neurons. In contrast, other neuropeptides - posterior pituitary hormone, but also TRH, a vasoactive intestinal peptide (VIP), substance P or endorphins - are also found in supernatant fractions. The existence of multiple molecular forms of neuropeptides is likely to explain these differences. Current theories postulate that they are synthetized on ribosomes as precursor forms. Their active structure is only achieved by enzymatic splitting of the pre- or the prohormone within nerve endings. This mode of synthesis is probably common to all neuropeptides, although it has only been well substantiated in a few cases, in particular for the hormones of the posterior pituitary. Thus, the lack of immunologically detectable LHRH or SRIF outside the synaptosomal fraction may reflect masking of the active immunological sites by inert peptide chains associated with prohormonal forms. Fractionation methods can also be applied to physiological or pharmacological experiments. In particular, they permit to characterize, on presynaptic membranes of neurosecretory neurons, specific receptors to neurotransmitters involved in the control of neurohormone secretion. Interaction of dopamine and acetylcholine with LHRH and CRF release are presented as examples of such applications.
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PMID:[Subcellular distribution of hypothalamic neurohormones and in vitro stimulation of their release]. 20 91

The Wobbler mouse possesses an inherited motoneuron disease, which expresses itself primarily at cervical spinal levels and in cranial motor nuclei. Cell degeneration is sporatic and negligible in other motor regions of the brain (e.g., cerebellum, corpus striatum). However, enkephalin concentrations are consistently lower in the Wobbler cerebellum throughout the motoneuron disease, whereas substance P concentrations are significantly higher late in the disease compared with the normal phenotype littermates. The data imply that early changes in enkephalin (also shown for leucine enkephalin in the spinal cord and brainstem) may be important to the etiology of the Wobbler disorder. Like the late increase of substance P, this may reflect a yet-to-be described response to parent cell degeneration in the raphe nuclei. TRH remained unchanged in Wobbler cerebellum and corpus striatum, wherein the other peptides studied herein also maintained similar concentrations to the normal phenotype littermates.
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PMID:Decrease of enkephalins in cerebellum during Wobbler mouse motoneuron disease. 128 61

It is now a recognized principle that various neuropeptides are neuronally co-localized with biogenic amine or aminoacid neurotransmitters. In the rat CNS it has previously been shown that TRH is co-localized with 5-HT (and also with substance P) in cell bodies of the posterior raphe that project to the spinal cord. Although TRH cell bodies are known to be widely distributed throughout the forebrain there is no other known co-localization with 5-HT. In this study we further specify the forebrain there is no other known co-localization with 5-HT. In this study we further specify the anatomical relationship of TRH with 5-HT by use of surgical and neurotoxic lesioning with reference to limbic forebrain regions wherein TRH is greatly increased following seizures. In groups of rats, the fimbria-fornix was lesioned alone, or combined with a lesion of the dorsal perforant path or the ventral perforant path. There was a sham lesioned control group. Additional groups were lesioned with 5,7 dihydroxytryptamine, 100 micrograms i.v.t., 45 min. after i.p. desipramine, 25 mg/kg. All rats were sacrificed three weeks after lesions. Indoleamines were determined by HPLC in left anterior cortex, left pyriform/olfactory cortex, left dorsal hippocampus and left ventral hippocampus. TRH was determined by specific RIA in the corresponding right brain regions. The modal n was 7 rats.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Some regional anatomical relationships of TRH to 5-HT in rat limbic forebrain. 138 39

There was no apparent difference in the regional distribution of neuropeptides in the brain of male and female rats. The highest levels of immunoreactive leu-enkephalin, TRH, substance P and somatostatin were found in the hypothalamus, while the striatum and the cerebral cortex had the highest concentrations of met-enkephalin and cholecystokinin respectively. The lowest concentrations of these were found in the cerebellum. Enkephalins (cerebral cortex), substance P (cerebral cortex and brain stem), and somatostatin (brain stem and striatum) showed higher level in the female while enkephalin and substance P contents in the anterior pituitary were higher in the male.
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PMID:The regional distribution of thyrotropin releasing hormone, leu-enkephalin, met-enkephalin, substance P, somatostatin and cholecystokinin in the rat brain and pituitary. 171 78

TRH is one of the first hypothalamic releasing hormones which has been identified and applied in humans. It is a tripeptidamid which belongs to the family of neuropeptides together with endorphins, neurotensin and substance P. TRH is widely distributed not only in hypothalamus, but also in extrahypothalamic parts of CNS as well as in many peripheral tissues and organs. TRH receptors are one of the first discovered peptide receptors in the brain. TRH coexists with other neurotransmitters and neuromodulators in brain neurons. In addition to its endocrine function in the regulation of TSH secretion, it also releases prolactin, FSH and NOR. Moreover, its extrapituitary actions have not yet been fully elucidated. Although TRH receptors are identified in CNS, it is not yet known whether it is a neurotransmitter or a neuromodulator. In particular, its relationship with cholinergic, noradrenergic, dopaminergic, serotonergic and opioid systems as well as other putative neurotransmitters in the brain, has been discussed. Finally, TRH is used as a diagnostic means in some endocrine and nonendocrine disorders.
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PMID:[Thyrotropin-releasing hormone: distribution, role and importance]. 180 96


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