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)

Bladder motility recordings were performed in anaesthetized rats and the effect of the peripherally active opiate agonist loperamide on urinary bladder function was studied. Regional intra-arterial administration of loperamide (0.01-2 mg kg-1) induced weak bladder contraction per se. Loperamide caused an effective dose-dependent inhibition of bladder motility induced by regional injection of the receptor agonists acetylcholine (ACh) and substance P (SP), as well as by peripheral motor nerve stimulation (PNS). Pretreatment with naloxone (0.5 mg kg-1) partially antagonized the inhibitory action of loperamide on the nerve-mediated detrusor contraction. However, the depression of the motor responses induced by the receptor agonists ACh and SP was not influenced. It is suggested that the demonstrated inhibitory effect of loperamide on bladder motility is partially mediated by peripheral opioid receptors. The main non-opioid part of the inhibition might be a direct smooth muscle action.
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PMID:In vivo motor effects of loperamide on the rat urinary bladder. 138 Feb 2

Substance P (SP), neurotensin (NT), bombesin (BB), serotonin (5HT), and carbamylcholine (CCH) transiently increase electrogenic anion secretion in chinchilla and chicken ileum. SP and CCH also transiently inhibit amiloride-sensitive Na/H exchange in isolated chicken enterocytes. Loperamide (LP) inhibits the short-circuit current responses caused by SP, NT, and BB, but not those caused by CCH, 5HT, Ca ionophore, or cyclic nucleotides. Similarly, LP inhibits the effects of SP, but not those of CCH, on Na/H exchange. LP inhibition of the SP effects was further studied in isolated chicken enterocytes. CCH and SP transiently increased cytosolic Ca activity by 20-50 nmol/liter, but only the response to SP was inhibited by LP (10(-5) M) and by the absence of extracellular Ca. We conclude SP and CCH effects on intestinal electrolyte transport are mediated by increasing enterocyte Ca activity and LP specifically inhibits peptide hormone-activated Ca entry by an opiate receptor-independent mechanism.
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PMID:Secretagogue-induced changes in membrane calcium permeability in chicken and chinchilla ileal mucosa. Selective inhibition by loperamide. 242 33

The effect of loperamide on tachykinin NK(2)- and NK(3)-receptor-mediated 5-HT outflow from guinea pig colonic mucosa was investigated in vitro. The selective tachykinin NK(2)-receptor agonist [beta-Ala(8)]-neurokinin A(4-10) (betaAla-NKA) or the selective NK(3)-receptor agonist senktide elicited an increase in 5-HT outflow from whole colonic strips, but not from mucosa-free muscle layer preparations. The enhancing effect of betaAla-NKA and senktide was prevented by the selective NK(2)-receptor antagonist GR94800 or the selective NK(3)-receptor antagonist SB222200. Loperamide concentration-dependently suppressed the senktide-evoked 5-HT outflow, but failed to affect the betaAla-NKA-evoked 5-HT outflow. The kappa-opioid receptor antagonist nor-binaltorphimine or the delta-opioid receptor antagonist naltrindole displaced the concentration-response curve for the suppressant action of loperamide to the right without significant depression of the maximum. However, the mu-opioid receptor antagonist CTOP did not affect the suppressant effect of loperamide. We concluded that the NK(3) receptor-triggered 5-HT release from colonic mucosa is suppressed by loperamide-sensitive mechanisms, whereas the NK(2)-receptor-triggered 5-HT release is loperamide-insensitive. Our data also suggest that the suppressant effect of loperamide is probably mediated by the activation of kappa- and delta-opioid receptors located on intrinsic neurons.
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PMID:Loperamide inhibits tachykinin NK3-receptor-triggered serotonin release without affecting NK2-receptor-triggered serotonin release from guinea pig colonic mucosa. 1594 25

The symptomatic management of irritable bowel syndrome (IBS) and functional dyspepsia, which often overlap, can be frustrating and difficult. Education and reassurance remain central for management although controlled trials are lacking. Psychological interventions may be useful in select patients but methodological inadequacies in clinical trials limit their interpretability. For symptom exacerbations, drug treatment is reasonable but no current treatment successfully targets the full symptom complex. Bulking agents are not of proven efficacy in IBS; they may improve constipation but worsen bloating and pain. Anticholinergics are of uncertain value in IBS. A meta-analysis of trials of smooth muscle relaxants for IBS has been reported to be positive but the quality of the trials included was poor. Antidepressants for IBS and functional dyspepsia appear to be efficacious based on the limited published evidence; both global symptoms and abdominal pain improve. Selective serotonin reuptake inhibitors (SSRIs) are of uncertain efficacy but anecdotally appear to be useful. Laxatives are not of proven efficacy in IBS. Loperamide improves diarrhea, but not abdominal pain in IBS. No drug is of proven efficacy for bloating. Acid suppression remains the mainstay of therapy for functional dyspepsia but the majority of patients do not have an adequate response. Promising drugs include new prokinetics for constipation-predominant IBS (e.g., tegaserod, a partial 5-HT4 agonist, prucalopride, a full 5-HT4 agonist, and dexloxiglumide, a cholecystokinin1 antagonist), agents for diarrhea-predominant IBS (e.g., 5-HT3 antagonists, alpha2 receptor agonists and corticotrophin receptor-1 antagonists), other visceral analgesics (e.g. tachykinin antagonists, opioid agonists) and in dyspepsia fundus relaxing agents (e.g., 5-HT1 agonists, tegaserod).
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PMID:New and emerging treatments for irritable bowel syndrome and functional dyspepsia. 1598 38