Substance P and Affective Disorders: New Treatment Opportunities by Neurokinin 1 Receptor Antagonists?

Lieb, Klaus; Treffurth, Yvonne; Berger, Thomas; Fiebich, Bernd L.

doi:10.1159/000049254

Cited by 28 publications

(21 citation statements)

References 36 publications

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“…Roles of other neurotransmission systems including cholinergic, amino acid (glutamate and GABA) and peptidergic neurotransmission in bipolar disorder or related physiological functions such as appetite and anxiety are also supported by neuropharmacological findings, [44][45][46][47][48] although not detailed here.…”

Section: Neurotransmission Systemsmentioning

confidence: 68%

Genetic tests of biologic systems in affective disorders

et al. 2005

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To liberate candidate gene analyses from criticisms of inexhaustiveness of examination of specific candidate genes, or incompleteness in the choice of candidate genes to study for specific neurobiological pathways, study of sizeable sets of genes pertinent to each putative pathophysiological pathway is required. For many years, genes have been tested in a 'one by one' manner for association with major affective disorders, primarily bipolar illness. However, it is conceivable that not individual genes but abnormalities in several genes within a system or in several neuronal, neural, or hormonal systems are implicated in the functional hypotheses for etiology of affective disorders. Compilation of candidate genes for entire pathways is a challenge, but can reasonably be carried out for the major affective disorders as discussed here. We present here five groupings of genes implicated by neuropharmacological and other evidence, which suggest 252 candidate genes worth examining. Inexhaustiveness of gene interrogation would apply to many studies in which only one polymorphism per gene is analyzed. In contrast to whole-genome association studies, a study of a limited number of candidate genes can readily exploit information on genomic sequence variations obtained from databases and/or resequencing, and has an advantage of not having the complication of an extremely stringent statistical criterion for association. Molecular Psychiatry (2005) 10, 719-740.

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Section: Neurotransmission Systemsmentioning

confidence: 68%

Genetic tests of biologic systems in affective disorders

et al. 2005

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“…Recent developments with substance P antagonists have demonstrated the importance of substance P in several models of disease including asthma, chronic bronchitis, cystitis, inflammatory bowel disease, migraine, emesis, depression, pain, and seizures (2,3,6,8,15,23,24,26,27,36,39). Using an in vitro model, the studies outlined in this paper demonstrate that some of the effects of cryptosporidiosis can be decreased with an SP receptor antagonist.…”

Section: Discussionmentioning

confidence: 82%

Substance P Is Responsible for Physiological Alterations Such as Increased Chloride Ion Secretion and Glucose Malabsorption in Cryptosporidiosis

et al. 2007

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Cryptosporidiosis, caused by the protozoan parasite Cryptosporidium, causes self-limited diarrhea in immunocompetent hosts and severe life-threatening diarrhea in AIDS patients. Highly active antiretroviral therapy has been used to effectively treat cryptosporiosis in some but not all AIDS patients. Therefore, there is an urgent need for innovative drugs to treat this disease. Cryptosporidium infection results in intestinal pathophysiological changes such as glucose malabsorption, increased chloride ion (Cl ؊ ) secretion, and epithelial barrier disruption, leading to disease pathogenesis. In order to develop tools to combat this opportunistic pathogen, it is vital to understand mediators involved in disease pathogenesis. Substance P (SP), a neuropeptide and pain transmitter, is located in the gastrointestinal tract. SP can cause Cl ؊ secretion in human gastrointestinal explants. However, its role in cryptosporidiosis has not been fully studied. Jejunal samples from macaques before and after Cryptosporidium parvum infection were assayed for SP and SP receptor mRNA and protein levels by reverse transcription-PCR and by immunohistochemistry and enzyme-linked immunosorbent assay, respectively. The role of SP in pathophysiological alterations, such as Cl ؊ secretion and glucose malabsorption, was studied using tissues derived from macaques infected with C. parvum by the Ussing chamber technique. SP and SP receptor mRNA and protein expression levels were increased in jejunal samples following C. parvum infection and were accompanied by increased basal ion secretion and glucose malabsorption. In vitro treatment of samples obtained from infected macaques with the SP receptor antagonist aprepitant (Emend; Merck, Whitehouse Station, NJ) completely reversed the increase in basal ion secretion and corrected the glucose malabsorption. Our findings raise the possibility of using SP receptor antagonists for the treatment of symptoms associated with cryptosporidiosis.

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“…As an interesting detail, hot peppers produce their characteristic effect because of their content of the active principle, capsaicin, which induces SP release (Holzer, 1987). Recently, SP was found to be involved in mental depression, and some SP antagonists with antidepressant properties have been developed (Lieb et al, 2002). In the digestive system, tachykinins stimulate salivary secretion and the peristaltic contractions in the intestines (Takeda & Krause, 1989;Holzer & Holzer-Petsche, 1997).…”

mentioning

confidence: 99%

Tachykinins and their possible modulatory role on testicular function: a review

2003

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Tachykinins are vasoactive and smooth muscle-contracting peptides with widespread localizations. Tachykinins have been localized in the nerve fibres that supply the testes, in the Leydig cells of different animal species, and also in Sertoli cells of the Siberian hamster testes. The presence of substance P (SP) has also been demonstrated in ejaculated human spermatozoa and in the seminal plasma. Tachykinins have been shown to inhibit the release of testosterone by testicular fragments or by isolated Leydig cells in vitro. Acting on Sertoli cells, tachykinins have been shown to stimulate the release of lactate and transferrin by these cells in vitro, and also to stimulate aromatase activity. Leydig and Sertoli cells express the Preprotachykinin A gene, and this fact strongly suggests that tachykinins can be synthesized in the testes. These findings suggest that tachykinins may have a physiological function in the testes as modulators of the functions of the different cell types contained in these organs.

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Substance P and Affective Disorders: New Treatment Opportunities by Neurokinin 1 Receptor Antagonists?

Cited by 28 publications

References 36 publications

Genetic tests of biologic systems in affective disorders

Genetic tests of biologic systems in affective disorders

Substance P Is Responsible for Physiological Alterations Such as Increased Chloride Ion Secretion and Glucose Malabsorption in Cryptosporidiosis

Tachykinins and their possible modulatory role on testicular function: a review

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