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

Progesterone (P) acts in the central nervous system to increase prolactin secretion in estrogen (E)-primed female monkeys. beta-Endorphin (BE) and Substance P (SP) are two hypothalamic peptides which increase prolactin secretion when administered to rats and monkeys. Studies were performed to determine if P acts on these two potential prolactin-releasing systems. The presence of a nuclear steroid receptor defines the cell as a target for the cognate hormone. Therefore, the hypothalamic populations of BE and SP neurons were examined for the presence and regulation of nuclear progestin receptors (PR) in spayed, E-treated (28 days) and E + P-treated monkeys (14 days E + 14 days E + P). Hypothalamic blocks were prepared after perfusion fixation with 4% paraformaldehyde. Cryosectioning (10 mu m) was followed by double immunocytochemistry (ICC) for PR (black nuclear stain) and either BE or SP (brown cytoplasmic stain). Sections were processed for ICC at 100- or 200-mu m intervals through the hypothalamic block. Peptidergic neurons with and without PR were counted in each section. The E + P-treated monkeys exhibited a significant increase in serum prolactin. BE neurons were found only in the arcuate nucleus (ARC) and median eminence (ME). The colocalization of BE and PR equaled 2% in spayed controls, 21% in the E-treated group and 25% in the E + P-treated group. SP neurons were located in a dorsomedial hypothalamic (DMH) subpopulation which extended caudally under the mamillary nuclei and in a subpopulation located in the ARC and ME. Neither the DMH or submamillary SP neurons contained PR. The percent colocalization of SP and PR in the ARC/ME equaled 5, 26 and 10% in the spayed, E- and E + P-treated groups, respectively. The decrease in PR + SP colocalization with P treatment is probably due to a decrease in SP and not to a decrease in PR immunoreactivity. In summary, E treatment induced PR in BE and SP neurons. Addition of P to the E treatment did not alter the expression of PR in BE neurons, but PR colocalization decreased in SP neurons. Therefore, it is unlikely that SP neurons could transduce the action of P on prolactin secretion in primates, but BE neurons may play an intermediary role.
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PMID:Immunohistochemical detection of progestin receptors in hypothalamic beta-endorphin and substance P neurons of steroid-treated monkeys. 905 77

Head-up tilt testing has become a valuable and widely accepted diagnostic tool for evaluation of patients with vasovagal syncope. This test has afforded clinical researchers the opportunity to focus on the hemodynamic, humoral, and neural changes that accompany syncope. We review the animal and clinical studies that provide insight into the possible pathophysiological mechanisms involved in vasovagal syncope. Hemodynamic measurements in patients with vasovagal syncope suggest that a relative decrease in ventricular size and increase in cardiac contractility may be seen in many patients with vasovagal syncope. Patients with vasovagal syncope have also demonstrated numerous "exaggerated" neurohumoral responses to syncope. Differential changes in plasma levels of epinephrine, renin, endothelin, vasopressin, cortisol, prolactin, beta endorphins, and substance P have been reported by some investigators either prior to or during a syncopal episode in patients with vasovagal syncope. The precise pathophysiological significance of these measurements is unknown at the present time. Measurements of autonomic tone may be accomplished indirectly with analysis of heart rate variability or baroreflex slope, or directly by sympathetic neural recordings of the peroneal nerve. We have demonstrated decreased baroreflex slopes in patients with vasovagal syncope. Using microneurography, we and others have demonstrated decreased sympathetic nerve activity occurring 11 +/- 3 seconds prior to syncope during head-up tilt table testing. A variety of other abnormal reflexes, including blunted forearm blood flow responses during exercise, have been demonstrated by others. These observations suggest that pacing instituted after the event may not be as helpful as the use of a hemodynamic sensor that will result in the initiation of pacing prior to sympathetic withdrawal or modify the decrease in sympathetic tone that occurs prior to syncope.
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PMID:Neural monitoring of vasovagal syncope. 908 May 11

The concept of neuro-immuno-cutaneous system (NICS) means narrow interrelations between nervous system, immunity and skin. Indeed, there are numerous cellular contacts between nerve fibers, cutaneous cells and immune cells; cutaneous cells can synthesize neuromediators and they express receptors to these molecules; neuromediators are able to modulate functions of cutaneous and/or immune cells. Using confocal or electron microscopy, connexions between nerve fibers and cutaneous cells have been observed. In the skin, nerve fibers may secrete neuromediators: substance P, vaso-active intestinal peptide (VIP), somatostatin, calcitonin-gene related peptide (CGRP), gastrin-releasing peptide (GRP), neuropeptide Y, peptide histidine-isoleucine (PHI), neurotensin, neurokinins A et B, bradykinin, acetylcholine, catecholamines, endorphins and enkephalins. Neurohormones such as prolactin, melano-stimulating hormone (MSH) or adreno-corticotrophic hormone (ACTH) are also expressed in the skin. Neuromediators and neurohormones are also secreted by cutaneous cells and these cells express receptors. Functions of epidermal or dermal cells are modulated by these substances. Immune cells transiently present in the skin (macrophages, lymphocytes...) are modulated by neuromediators through receptors. In the course of skin diseases, especially inflammatory diseases, the NICS is destabilized. Psoriasis and atopic dermatitis are good examples. This phenomenon might be due to inflammation but is also responsible for induction and maintenance of the inflammation.
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PMID:[Neuro-immuno-cutaneous system (NICS)]. 915 66

The present study deals with the effects of withdrawal of dopamine (DA) on the translocation of protein kinase C (PKC) isozymes and release of prolactin (Prl) in resting- and substance P (SP)-stimulated cultures of enriched rat pituitary lactotrophs. Following a brief tonic input (10 min), DA withdrawal induced a redistribution of PKC alpha- and beta-immunoreactivity (IR) to the particulate fraction with maximal levels, attained after 5 min, remaining translocated for 20 min. DA withdrawal prolonged the effect of SP-induced translocation of PKC alpha- and beta-IR. Similar effects were detected when the catalytic activity of PKC in response to DA withdrawal was evaluated. Thus, DA washout redistributed PKC catalytic activity and prolonged the effect of SP on catalytical PKC translocation to the particulate fraction. Pretreatment of cells with the protein kinase A inhibitor, rp-adenosine-3',5'-cyclic monophosphothionate (rp-cAMP), reduced the amount of PKC alpha- and beta-IR redistributed after DA withdrawal. Furthermore, this treatment also reduced the DA withdrawal effect on SP-mediated translocation of PKC alpha- and beta-IR. Methoxyverapamil, a blocker of voltage-gated Ca2+ channels, completely inhibited the redistribution of PKC isozymes after DA withdrawal, but also reduced the potentiating effect of DA withdrawal on SP-induced redistribution of PKC isozyme-IR. In perifused enriched lactotrophs, DA withdrawal induced a release of Prl that lasted 45-55 min and prolonged the effect of SP on Prl secretion. rp-cAMP did not significantly affect Prl release due to DA removal, but the prolonging effect of DA withdrawal on SP-induced Prl secretion was abolished. Methoxyverapamil completely abolished the rebound release of Prl after DA withdrawal, and the potentiating effect of DA removal on SP-mediated Prl release was also diminished. Readdition of DA after DA withdrawal was able to suppress the translocation of PKC isozyme-IR and catalytic activity and to reduce the release of Prl to baseline levels. Moreover, readdition of DA reduced the potentiating effects of DA withdrawal on the same parameters after SP-stimulation of cells. On the basis of these results it is concluded that in resting cells following DA withdrawal prolactin is released and specific PKC isozymes and concomitant catalytic activity are translocated to the particulate fraction in enriched lactotrophs. While cAMP/PKA and influx of Ca2+ seem to work in concert in translocating PKC, influx of Ca2+ is the primary mechanism responsible for the rebound release of Prl after DA withdrawal. DA withdrawal exerts a potentiating effect on SP-induced PKC translocation and Prl release. It is suggested that the biochemical events involved in these processes are cAMP/PKA and Ca2+ influx.
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PMID:Effects of withdrawal of dopamine on translocation of protein kinase C isozymes and prolactin secretion in rat lactotroph-enriched pituitary cells. Modulation of substance P-mediated responses. 919 72

Tachykinins are present in the anterior pituitary gland and there is evidence that they may have a direct intrapituitary role influencing the secretion of some of the hormones released by this gland. In this investigation, we have studied the effect of the non-peptide NK-2 receptor antagonist SR 48,968 (Sanofi Recherche) on the basal release of LH, FSH, and prolactin by rat hemipituitaries incubated in vitro, and also on the response to GnRH. SR 48,968 significantly inhibited prolactin release into the medium. The highest doses of this compound stimulated the basal release of LH by hemipituitaries from castrated, castrated testosterone-treated, and ovariectomized estradiol-treated rats, but not from intact male rats. SR 48,968 significantly inhibited the release of LH in response to GnRH. Since some tachykinin receptor antagonists have been demonstrated to act also on calcium channels, studies with verapamil, a calcium channel antagonist, were also carried out for comparison. Verapamil inhibited prolactin release into the medium and decreased the LH response to GnRH. These results suggest that tachykinins that bind NK-2 receptors, may have an intrapituitary role stimulating the release of prolactin, and that they may also modulate the response of the gonadotrophs to GnRH. The fact that verapamil shares some of the actions exerted by NK-2 receptor antagonists on the pituitary glandm however, suggests the possibility that some of the effects of NK-2 receptor antagonists may be mediated through calcium channel antagonism. Therefore, the results observed with the use of some of these antagonists should be interpreted with great caution.
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PMID:Effect of a non-peptide NK-2 tachykinin receptor antagonist on LH, FSH, and prolactin release by rat hemipituitaries in vitro. 937 29

Connections between nerve fibres and cutaneous cells have been studied using confocal and electron microscopy. In the skin, nerve fibres may secrete neuromediators, i.e. substance P, vasoactive intestinal peptide, somatostatin, calcitonin-gene-related peptide, gastrin-releasing peptide, neuropeptide Y, peptide histidine-isoleucine, neurotensin, neurokinins A and B, bradykinin, acetylcholine, catecholamines, endorphins and enkephalins. Neurohormones such as prolactin, melanocyte-stimulating hormone and adrenocorticotrophic hormone are also expressed in the skin. Neuromediators and neurohormones may be secreted by cutaneous cells, which also express receptors. Functions of epidermal and dermal cells are modulated by these substances. Immune cells transiently present in the skin (e.g. macrophages and lymphocytes) are modulated by neuromediators through receptors. During the course of skin disorders, especially inflammatory reactions, the neuroimmunocutaneous system is destabilized. This is particularly true in psoriasis. This destabilization may be secondary, although evidence shows it can also be responsible for the induction and maintenance of the inflammatory process. The skin, the nervous system and immunity are not independent systems but are closely associated and use the same language of cytokines and neurotransmitters. A new concept is suggested: the neuroimmunocutaneous system.
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PMID:Skin, immunity and the nervous system. 947 Aug 98

It is well known that transgenic mice expressing bovine growth hormone have altered neuroendocrine functions. Substance P was shown to influence the secretion of gonadotropins. In this investigation, the effect of a single injection of an antiserum to substance P was investigated in intact and castrated transgenic (MT-bGH) mice and in their normal litter mates. In the median eminence, the administration of antisubstance P serum resulted in a decreased dihydroxyphenyl acetic acid/dopamine index in intact and castrated normal mice but was without effect in transgenics. The homovanillic/dopamine index was decreased in normal mice (intact or castrated) but unchanged in transgenics. Norepinephrine and epinephrine were increased in normal mice (intact and castrated) treated with the anti-SP serum, but in transgenic mice, the anti-SP serum induced significant changes of norepinephrine only in intact animals, with no modifications in epinephrine levels. In the whole hypothalamus (minus the median eminence), the injection of antisubstance P serum resulted in an increased dihydroxyphenyl acetic acid/dopamine index in castrated, but not in intact, normal mice. In transgenic mice, this index was increased in intact but decreased in castrated animals. The homovanillic/dopamine index was decreased in normal intact mice treated with the antiserum but increased in intact transgenic mice. Norepinephrine and epinephrine were decreased by the antiserum treatment in normal intact mice but were unchanged in transgenics, except for norepinephrine in castrated transgenics, in which it was found increased. The administration of the antiserum did not affect plasma LH, FSH, or prolactin in normal mice but it reduced LH levels in intact transgenic mice. These results indicate that the response to the treatment with the antiserum to substance P shows considerable alterations in transgenic mice as compared with their litter-mate, normal controls, producing divergent effects on hypothalamic catecholamine metabolism. The present findings confirm that transgenic mice overexpressing the bGH gene have marked neuroendocrine alterations as compared with their normal litter mates.
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PMID:Effects of immunoneutralization of substance P on hypothalamic neurotransmitters in normal mice and in transgenic mice expressing bovine growth hormone. 957 54

A novel G-protein-coupled receptor (GRL106) resembling neuropeptide Y and tachykinin receptors was cloned from the mollusc Lymnaea stagnalis. Application of a peptide extract from the Lymnaea brain to Xenopus oocytes expressing GRL106 activated a calcium-dependent chloride channel. Using this response as a bioassay, we purified the ligand for GRL106, Lymnaea cardioexcitatory peptide (LyCEP), an RFamide-type decapeptide (TPHWRPQGRF-NH2) displaying significant similarity to the Achatina cardioexcitatory peptide (ACEP-1) as well as to the recently identified family of mammalian prolactin-releasing peptides. In the Lymnaea brain, the cells that produce egg-laying hormone are the predominant site of GRL106 gene expression and appear to be innervated by LyCEP-containing fibers. Indeed, LyCEP application transiently hyperpolarizes isolated egg-laying hormone cells. In the Lymnaea pericardium, LyCEP-containing fibers end blindly at the pericardial lumen, and the heart is stimulated by LyCEP in vitro. These data confirm that LyCEP is an RFamide ligand for GRL106.
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PMID:The lymnaea cardioexcitatory peptide (LyCEP) receptor: a G-protein-coupled receptor for a novel member of the RFamide neuropeptide family. 982 40

We have previously reported that neurokinin A (NKA), a tachykinin closely related to substance P, increases the release of prolactin (PRL) from the anterior pituitary gland of male rats, but not from pituitaries of ovariectomized (OVX) female rats. In this study, we evaluated the influence of estrogens in the action of NKA on PRL secretion in female rats. NKA stimulated the in vitro release of PRL from pituitary glands of OVX-chronically estrogenized rats, and of proestrus and estrus rats, but had no effect in anterior pituitaries of diestrus rats. In addition, we observed that cultured anterior pituitary cells of OVX rats responded to NKA only when they were incubated for 3 days in the presence of estradiol 10(-9) M. This effect was blocked by L-659,877, an NK-2 receptor antagonist. We also studied the action of NKA on PRL release during lactation. The response of anterior pituitary cells to NKA was variable over this period. The maximal sensitivity to NKA was observed at day 10 of lactation. Furthermore, the blockade of endogenous NKA by the administration of an anti-NKA serum to lactating rats reduced the PRL surge induced by the suckling stimulus. These results show that the responsiveness of the anterior pituitary gland of female rats to NKA is modulated by the endocrine environment, and suggest that NKA may participate in the control of PRL secretion during the estrus cycle and lactation.
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PMID:The hormonal status modulates the effect of neurokinin A on prolactin secretion in female rats. 983 56

Modulation of the hypothalamo-pituitary-gonadal axis and the pineal gland by neurokinin A, neuropeptide K, and neuropeptide gamma. PEPTIDES 1999. Neurokinin A (NKA), neuropeptide K (NPK) and neuropeptide gamma (NPG) are members of the family of tachykinins, and act preferentially on NK-2 tachykinin receptors. These peptides are widely distributed and are potent stimulators of smooth muscle contraction, especially in the respiratory and gastrointestinal tract. They also induce vasodilatation and plasma extravasation. Through their effects on the vascular tone, they are also potential regulators of the blood flow and therefore of the function of many organs and tissues. Tachykinins have been demonstrated to influence the secretory activity of endocrine cells, and they may have a physiological role as regulators of endocrine functions. A number of reports have indicated that NPK, NKA and NPG act on the hypothalamo-pituitary gonadal axis to regulate functions related to reproduction. Therefore, we thought that, at this point, it was important to review the available evidence suggesting the role of these tachykinins on reproductive functions by effects exerted at 3 different levels of regulation: the hypothalamus, the anterior pituitary and the gonads. These 3 tachykinin peptides were reported to have effects on reproductive functions, acting on the control of the secretion of gonadotropin and prolactin at the level of the hypothalamo-pituitary axis, and on the steroid secretion by the testes and the ovaries. Acting on the hypothalamus, tachykinins, mainly NPK, were reported to inhibit LH secretion, but this effect is dependent on the presence of gonadal steroids. On the anterior pituitary gland, however, tachykinins were shown to stimulate LH and prolactin secretion, and this effect is also dependent on the presence of gonadal steroids. Tachykinin concentrations in the hypothalamus and pituitary are regulated by steroid hormones. In the hypothalamus, estrogens and testosterone increase tachykinin concentration. In the anterior pituitary gland, estradiol and thyroid hormones markedly depress tachykinin concentrations. Ovariectomy and exposure to short photoperiods significantly increase anterior pituitary tachykinins in the Siberian hamster. In the pineal gland, SP and NK-1 receptors are present and, more recently, the presence of NKA and probably also NPK was demonstrated. Castration and steroid replacement modified the content of tachykinins in the pineal gland. The removal of the superior cervical ganglia was followed by an increase in NKA content in the pineal gland. These results suggest that gonadal steroids may influence tachykinins in the pineal gland. In the gonads, tachykinins stimulated the secretory activity of Sertoli cells, but inhibited testosterone secretion by Leydig cells. There are very few reports on the role of tachykinins in the ovary, but some of them indicated that these peptides are present in some of the ovarian structures, and they may affect the secretion of ovarian steroids. Thus, NKA, NPK and NPG appear to have a modulatory role, mainly acting as paracrine factors, on the hypothalamo-pituitary-gonadal axis.
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PMID:Modulation of the hypothalamo-pituitary-gonadal axis and the pineal gland by neurokinin A, neuropeptide K and neuropeptide gamma. 1042 85


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