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

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

Progestin receptor-containing cells in the hypothalamus of the adult female green monkey (Cercopithecus aethiops) were examined by double-label immunocytochemical methods to determine their anatomical location, neurotransmitter content and afferent connections. Animals were ovariectomized and administered either estradiol valerate or the oil injection vehicle, and were sacrificed after 10 days of treatment. Using a monoclonal antibody raised against rabbit uterine progestin receptor (PR), the distribution of PR-immunoreactive cells in the mediobasal hypothalamus and the effect of estrogen treatment on this distribution was determined. PR-immunoreactive cells were found throughout the ventromedial nucleus (VMN), in the area between the VMN and fornix, and in the medial portion of the infundibular nucleus. Estrogen treatment dramatically increased both the number of labeled cells and the intensity of immunoreaction product in these regions. In double-immunostained sections, boutons immunoreactive for antigens indicative of serotonin, pro-opiomelanocortin derived peptides, GABA, catecholamine, neuropeptide Y, substance P, cholecystokinin, and somatostatin were demonstrated to establish synaptic contact with the soma of PR-immunoreactive hypothalamic neurons. In colchicine-pretreated animals, all PR-containing neurons in the mediobasal hypothalamus were found to contain immunoreactivity for glutamic acid decarboxylase, the enzyme required for synthesis of GABA. No evidence of colocalization with other antigens, including LHRH, was observed. Because LHRH neurons are known to receive a rich GABAergic innervation PR-containing GABAergic cells may represent steroid-sensitive sites of integration for inputs from other neural systems involved in the control of gonadotropin secretion.
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PMID:Transmitter content and afferent connections of estrogen-sensitive progestin receptor-containing neurons in the primate hypothalamus. 135 61

Tachykinins, a family of biologically active related peptides, are found in variable amounts in the rat hypothalamus. We assessed the effects of five tachykinins, substance P (SP), neurokinin A (NKA), neuropeptide K (NPK), neuropeptide gamma (NP gamma), and neurokinin B (NKB), on LH release in different experimental model systems in ovariectomized rats. In the first series of experiments rats were ovariectomized and implanted with permanent cannulae in the third cerebroventricle of the rat brain. Two weeks later, the effects of intracerebroventricular injection of 0.5 or 1.25 nm various tachykinins on LH release were studied. The results showed that whereas SP, NKA, and NKB were ineffective, and NP gamma was marginally effective, NPK produced a long-lasting suppression of LH release. NPK decreased LH release in a dose- and time-related fashion. Similarly, in the second series of experiments, whereas SP and NKA were inactive, NPK completely suppressed the LH surge induced by progesterone in estrogen-primed ovariectomized rats. In the third series of experiments we observed that NK-2 receptor agonist [Nle10]NKA4-10, and not NK-1 receptor agonist [Sar9,Met(O2)11]SP, suppressed both the release of LH in vivo and basal and KCl-induced hypothalamic LHRH release in vitro. These results show that NPK is the most effective tachykinin in suppressing LH release, and the inhibitory response is mediated by hypothalamic NK-2 receptors. These findings are in accord with the hypothesis that NPK may serve as a hypothalamic inhibitory neurotransmitter/neuromodulator of LHRH secretion.
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PMID:Effects of tachykinins on luteinizing hormone release in female rats: potent inhibitory action of neuropeptide K. 137 55

Neuropeptides are known to modulate the excitability of frog sympathetic neurons by inhibiting the M-current and increasing the leak current, but their effects on Ca2+ channels are poorly understood. We compared effects of LHRH, substance P, epinephrine, and muscarine on Ca2+, K+, and leak currents in dissociated frog sympathetic neurons. At concentrations that inhibit M-current, LHRH and substance P strongly reduced N-type Ca2+ current and induced a leak conductance that may contribute to slow EPSPs. In contrast, muscarine produced little reduction of Ca2+ current, even in cells in which it strongly suppressed the M-current. We find that peptidergic inhibition of Ca2+ channels involves G proteins, but does not require protein kinases. In addition, it leads to reductions in Ca2(+)-activated K+ current and catecholamine release.
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PMID:Inhibition of Ca2+ and K+ channels in sympathetic neurons by neuropeptides and other ganglionic transmitters. 169 May 65

The present studies were designed to evaluate the role of substance P (SP) in the control of the release of luteinizing hormone (LH), follicle stimulating hormone (FSH) and prolactin (PRL). SP was microinjected into the medial preoptic area (MPOA) of conscious, freely moving intact or orchidectomized (ORCX; 21 days post-ORCX) adult male rats. Microinjection of SP into the MPOA induced a significant decrease in plasma LH and FSH concentrations, effects which were accompanied by an elevation in plasma PRL concentration. To examine the participation of endogenously secreted SP in the activity of the MPOA neurons controlling release of these cited pituitary hormones, another study was performed in which either a potent and specific antagonist to SP (D-Pro2, D-Trip7,9-SP; SP-ANT) or an antibody against SP (SP-AB), was injected into the MPOA. SP-ANT and SP-AB both elevated plasma LH, FSH and decreased plasma PRL concentration. These data suggest that endogenous SP within the MPOA exerts an important inhibitory tonus over LH and FSH release and an excitatory tonus over PRL release. In conclusion, SP seems to participate as a neurotransmitter or neuromodulater in the control of LH, FSH and PRL secretion, at least in part, by acting at the level of MPOA, a region in which the neuronal cell bodies that produce LH-releasing hormone and the associated gonadotropin-releasing hormone-associated peptide are located.
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PMID:Role of substance P in the medial preoptic area in the regulation of gonadotropin and prolactin secretion in normal or orchidectomized rats. 169 73

The effects of neonatal exposure to delta-9-tetrahydrocannabinol (THC) on the adult animal brain neurochemistry and pain perception were evaluated. Newborn rat pups were culled to a litter size of 8 (males and females) and treated either with THC (2 mg/kg) or oil (control) daily, during days 1-4 after birth. After weaning, the THC-treated males were housed 4 per cage. During the juvenile period (day 50), the THC-treated animals exhibited significantly lower baseline tail-flick values (a measure of pain perception) than the control. However, as adults, the THC-treated animals exhibited significantly higher sensitivity to pain following 5 mg/kg morphine challenge. Furthermore, the THC-treated animals had significantly elevated beta-endorphin and methionine-enkephalin levels in almost all the brain areas sampled for the study. In addition, the neonatally THC-treated rats exhibited significantly higher levels of substance P (SP) and significantly lower levels of gonadotropin releasing hormone (GnRH) in the anterior hypothalamus-preoptic area. The SP and GnRH levels did not differ among the THC-treated and control animals in the medial basal hypothalamus. The results of this study indicate that even a very low dose of THC administered during the neonatal period has a long-lasting effect on the brain neurochemistry. In particular, neonatal administration of THC appears to alter functioning of the endogenous opioid system.
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PMID:Effect of early exposure to delta-9-tetrahydrocannabinol on the levels of opioid peptides, gonadotropin-releasing hormone and substance P in the adult male rat brain. 170 Sep 26

The distribution of substance P (SP), gonadotropin releasing hormone (GnRH) and Met-enkephalin in the brain and spinal cord of the domestic pig is described for the first time. The levels of SP, GnRH and Met-enkephalin were measured by specific radioimmunoassays in various regions of the brain and spinal cord of the pig. Substance P and Met-enkephalin are widely distributed within the central nervous system of the pig. High levels of SP were found in the preoptic area (POA), suprachiasmatic area (SCA), medial basal hypothalamus (MBH) and brain stem while moderate amounts of SP were found in olfactory bulb (OB). High levels of Met-enkephalin were found in POA, SCA and MBH, and moderate levels of Met-enkephalin in OB and brain stem. Both SP and Met-enkephalin levels were higher in the dorsal spinal cord in comparison with the levels of these peptides in the ventral spinal cord. This finding is in agreement with the predominant role played by these neural systems in primary afferent mediation of nociceptive impulses. The POA and SCA contained only low levels of GnRH while the MBH contained high levels of GnRH. Finally, some differences in the quantitative distribution of these peptides in the pig and rat are discussed.
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PMID:Distribution of substance P, GnRH, Met-enkephalin in the central nervous system of the pig. 171 37

Our investigations of the four tachykinines tested have shown that NPK characteristically evoked a spectrum of biological effects in male and female rats. NPK suppressed pituitary LH release by inhibiting the release of hypothalamic LHRH, presumably by activation of NK-2 tachykinin receptor subtypes. However, NPK may also act at the level of gonadotrophs to stimulate LH release in male rats. Central injection of NPK rapidly disrupted copulatory behavior in sexually active male rats. NPK also suppressed feeding, but, in this case, peripheral injections were more effective than central injections. Taken together, these observations strongly imply that NPK may be an inhibitory messenger molecule in the hypothalamic control of reproduction, sexual, and feeding behaviors.
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PMID:Effects of various tachykinins on pituitary LH secretion, feeding, and sexual behavior in the rat. 171 76

Many studies have indicated that nitrous oxide (N2O) exposure results in specific effects on the reproductive system, some of which are antigonadotropic. The neurochemical events regulating the pituitary-gonadal axis are probably influenced by N2O, but precise documentation is lacking. The effects of exposure to 30% N2O in air on the brain tissue concentrations of luteinizing hormone releasing hormone (LHRH), substance P (SP), met-enkephalin, and beta-endorphin and on beta-endorphin concentrations of the pituitary gland are described in this study. Female rats were exposed to either N2O or air for 8 hr a day over one estrous cycle, and the brain and pituitary tissues were collected and processed. Neuropeptide concentrations were measured by specific radioimmunoassays. Exposure to N2O resulted in significant elevation of LHRH in the preoptic area, with a concomitant decrease in SP. The SP concentration of the medial basal hypothalamus was significantly elevated in N2O-exposed animals. Exposure to N2O resulted in significant increases in met-enkephalin in the brainstem area and beta-endorphin in the pituitary. These results suggest that exposure to N2O alters the interactive neural system activity regulating gonadotropin secretion from the pituitary. The significance of increased met-enkephalin in the brainstem of N2O-exposed animals is not known.
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PMID:Effect of nitrous oxide on the concentrations of opioid peptides, substance P, and LHRH in the brain and beta-endorphin in the pituitary. 172 17


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