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)

Cells of the immune system synthesize prolactin and express mRNA and receptors for that hormone. Interleukin 1, interleukin 6, gamma interferon, tumor necrosis factor, platelet activator factor, and substance P participate in the release of prolactin. This hormone is involved in the pathogenesis of adjuvant arthritis and restores immunocompetence in experimental models. In vitro studies suggest that lymphocytes are an important target tissue for circulating prolactin. Prolactin antibodies inhibit lymphocyte proliferation. Prolactin is comitogenic with concanavalin A and induces interleukin 2 receptors on the surface of lymphocytes. Prolactin stimulates ornithine decarboxylase and activates protein kinase C, which are pivotal enzymes in the differentiation, proliferation, and function of lymphocytes. Cyclosporine A interferes with prolactin binding to its receptors on lymphocytes. Hyperprolactinemia has been found in patients with systemic lupus erythematosus. Fibromyalgia, rheumatoid arthritis, and low back pain patients present a hyperprolactinemic response to thyrotropin-releasing hormone. Experimental autoimmune uveitis, as well as patients with uveitis whether or not associated with spondyloarthropathies, and patients with psoriatic arthritis may respond to bromocriptine treatment. Suppression of circulating prolactin by bromocriptine appears to improve the immunosuppressive effect of cyclosporine A with significantly less toxicity. Prolactin may also be a new marker of rejection in heart-transplant patients. This body of evidence may have an impact in the study of rheumatic disorders, especially connective tissue diseases. A role for prolactin in autoimmune diseases remains to be demonstrated.
 ...
PMID:Prolactin, immunoregulation, and autoimmune diseases. 206 74

The effects of cyclosporin A on the occurrence of neuroendocrine peptides in bone induced by demineralized allogeneic and xenogeneic bone matrix were studied in rats. Cyclosporin A enhanced bone induction in demineralized allogeneic bone matrix implants by 40% to 50% at 4 weeks, whereas there was no difference to the control group at 8 weeks. In demineralized xenogeneic bone matrix implants there was virtually no cartilage or bone formation at 4 weeks, but some bone and cartilage formation was seen at 8 weeks. In both cyclosporin A treated groups the net bone formation in demineralized xenogeneic bone matrix implants was increased four to five times at 4 weeks. Cyclosporin A treatment did not alter the temporal occurrence or distribution of neuropeptide containing nerve fibers in the bone induced by allogeneic bone matrix. Fibers containing substance P, calcitonin gene related peptide, neuropeptide Y, vasoactive intestinal peptide, and tyrosine hydroxylase were detected in the ossicles of cyclosporin A treated and control rats. In the xenogeneic bone matrix of the control group, no immunoreactive nerve fibers could be detected at 4 weeks, but at 8 weeks all five neuropeptides were detected. However, after cyclosporin A treatment immunoreactive nerve fibers could be seen at 4 weeks in the demineralized xenogeneic bone matrix implants. Thus, immunologic properties of the inductive matrix affect the yield of mineralized bone and the degree of innervation. Cyclosporin A decreases the immune response and enhances the formation of bone and the number of transmitter identified nerves in demineralized xenogeneic bone matrix induced ossicles.
 ...
PMID:Neuropeptides in heterotopic bone induced by bone matrix in immunosuppressed rats. 941 45

We have investigated the contractile property of cyclosporin A and FK506 in guinea-pig isolated bronchus. Cyclosporin A (10 microM) failed to significantly attenuate the excitatory non-adrenergic non-cholinergic (eNANC) and cholinergic contractile response (per cent methacholine Emax) induced by electrical field stimulation (EFS). In contrast, eNANC responses were significantly attenuated by both the neurokinin (NK)-1 and (NK)-2 receptor antagonists, N-acetyl-L-tryptophan 3,5-bis (trifluoromethyl)-benzyl and SR48968, respectively. Cyclosporin A and FK506 caused a concentration-dependent contraction in guinea-pig isolated bronchus, which was significantly attenuated by NK-1 and NK-2 receptor antagonists. The capsaicin receptor antagonist, capsazepine (10 microM) significantly reduced the contractile response to cyclosporin A and capsaicin, but not to FK506. The N-type calcium channel blocker, omega-Conotoxin (omegaCTX: 10 nM), significantly reduced the contractile response to FK506 and the eNANC response following EFS. In contrast, omega-CTX failed to significantly reduce the contractile potency to capsaicin or cyclosporin A. In bronchial preparations desensitized by repeated application of capsaicin (1 microM), the contractile responses to both cyclosporin A (100 microM) and FK506 (100 microM), were significantly reduced. In contrast, the contractile responses to substance P and neurokinin A (10 microM) were not altered. Furthermore, repeated application of cyclosporin A (100 microM) significantly inhibited the contractile response to capsaicin (1 microM). The findings from this study would indicate that cyclosporin A and FK506 mediate contraction of guinea-pig isolated bronchus secondary to the release of neuropeptides from airway sensory nerves. However, the release of sensory neuropeptides appears to be mediated via different mechanisms for cyclosporin A and FK506, the former by stimulation of the vanilloid receptor and the latter via opening of N-type calcium channels.
 ...
PMID:Stimulation of airway sensory nerves by cyclosporin A and FK506 in guinea-pig isolated bronchus. 988 67

Cyclosporin A, an immunosuppressant, has the potential to increase tear fluid secretion through mechanisms which are not yet well understood. To gain insight into this question, we investigated the effect of cyclosporin A containing eyedrops on lacrimation in normal mice. Topical application of 0.1% cyclosporin A eyedrops for 3 days significantly increased lacrimation. This response was completely blocked by pre-exposure to 1% capsaicin. Immunohistochemical analysis revealed that capsaicin treatment depleted substance P from the lacrimal gland. Furthermore, following 1% atropine treatment, which completely blocks pilocarpine-stimulated (500 micrograms kg-1, i.p.) lacrimation, application of 0.1% cyclosporin A eyedrops significantly increased lacrimation. However, this increase was less than the response seen with 0.1% cyclosporin A in the absence of atropine. Interestingly, substance P-induced tear secretion was also partially inhibited in atropine treated mice. These results suggest that cyclosporin A accelerates tear secretion by releasing neurotransmitters from sensory nerve endings which interacts with the parasympathetic nerves.
 ...
PMID:Cyclosporin A increases tear fluid secretion via release of sensory neurotransmitters and muscarinic pathway in mice. 1032 67

1. Although a number of interventional pharmacotherapies have undergone clinical trial in traumatic brain injury (TBI), none has shown considerable promise. The present short review will examine some of the more novel compounds that have been proposed recently as potential therapeutic agents for use in TBI. 2. Previous experimental studies have demonstrated that brain intracellular free magnesium significantly declines following TBI and that the administration of magnesium salts attenuates the post-traumatic neurological deficits. More recent studies have established that magnesium salts administered after trauma enter the brain intracellular space and reduce the size of the lesion volume. Such protection could be afforded through attenuation of both necrotic and apoptotic cell death. Magnesium salts are currently on clinical trial in TBI. 3. Cyclosporine A is known to inhibit opening of the mitochondrial permeability transition pore. Administration of cyclosporine A after TBI has been shown to attenuate axonal injury and decrease the resultant lesion volume. Therefore, inhibitors of mitochondrial transition pore opening and resultant attenuation of apoptosis show some promise as neuroprotective agents. 4. Recent evidence has shown that substance P antagonists may decrease lesion volume and improve neurological outcome after ischaemia. Similar findings have recently been reported in TBI. The fact that substance P antagonists are known to reduce neurogenic inflammation, oedema formation and are clinically being trialed as both antidepressants and antinociceptive agents suggests that these agents warrant further investigation as therapeutic agents following TBI. 5. There are numerous contradictions in the literature regarding the potential neuroprotective effects of the hormones oestrogen and progesterone. Recent studies suggest that both hormones are protective in TBI and further studies are required to ascertain the mechanisms associated with this protection and any potential for clinical application.
 ...
PMID:An overview of new and novel pharmacotherapies for use in traumatic brain injury. 1170 96

Cyclosporin A (CsA) is an immunosuppressive drug. In human cancer cells substance P (SP) and neurokinin-1 (NK-1) receptor antagonists, respectively, induce cell proliferation and inhibition. CsA is a tachykinin receptor antagonist that showed selectivity for both NK-1 and NK-2 receptors. CsA exerts antitumor action against gastric (AGS) and colon (HT29) carcinoma cell lines. However, the mechanisms involved in this action remain unknown, and it is unknown whether CsA exerts an antitumor action on other human cancer cell lines or not. To demonstrate that CsA exerts a broad-spectrum antitumor action, we carried out an in vitro study of the growth-inhibitory capacity of CsA against seven human cancer cell lines, namely GAMG glioma, SKN-BE(2) neuroblastoma, WERI-Rb-1 retinoblastoma, HEp-2 larynx carcinoma, CAPAN pancreas carcinoma, 23132/87 gastric carcinoma, and SW-403 colon carcinoma. A Coulter counter was used to determine viable cell numbers followed by application of the MTS colorimetric method. Micromolar concentrations of CsA inhibited the growth of these tumor cells, both with and without previous administration of nanomolar concentrations of SP; the inhibition occurred in a dose-dependent manner. Moreover, CsA blocks SP-induced mitogen stimulation of tumor cells, suggesting that the NK-1 receptor is involved in such action. Following administration of CsA apoptosis was observed in the above seven tumor cell lines. These findings suggest that the antitumor action of CsA is at least due to its NK-1 receptor antagonist pharmacological profile, since the involvement of NK-2 receptors in the mentioned action must not be discarded, and that CsA has a broad-spectrum antitumor action.
 ...
PMID:The broad-spectrum antitumor action of cyclosporin A is due to its tachykinin receptor antagonist pharmacological profile. 2054 69