Existing models used to study the mechanism of action and antagonism of tachykinergic effects on intestinal contraction and secretion suffer from technical problems and have not been fully characterized using specific tachykinin antagonists. Contraction of ileal segments by substance P, colonic circular muscle by beta-alanine-neurokinin A, and longitudinal muscle by senktide were used as models for neurokinin-induced contraction in the guinea-pig. Guinea-pig colonic epithelial tissue was stimulated by substance P and senktide to assess NK1- and NK3-mediated secretion. Using these models the potency of therapeutically useful compounds was determined. NK1 and NK2 activation directly contracted smooth muscle, while NK1-mediated secretion was nerve-mediated. NK3 stimulation of contraction and secretion was neurally mediated, involving cholinergic nerves and 5-HT release. NK1-mediated contraction and secretion were antagonized by SR140333 (pD'2 = 9.29 and pKb = 8.53); NK2-mediated contraction was antagonised by SR48968 (pD'2 = 8.35) and NK3-mediated contraction and secretion were antagonized by SB223412 (pKb = 8.97 and 8.79). The mixed antagonist MDL103392 blocked NK1- and NK2-mediated contraction with pKb values of 7.92 and 6.71 respectively and NK1-mediated secretion with a pKb value of 6.57. This data characterizes existing tachykinin antagonists, and should orientate the development of improved compounds as therapies for intestinal disease.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1211/0022357991773375 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Systemic calcinosis in horses: Pathological and genetic aspects.
Equine Vet J
January 2025
Setor de Patologia Veterinária, Universidade Federal Do Rio Grande Do Sul, Porto Alegre, RS, Brazil.
Background: In horses, systemic calcinosis is a rare syndrome characterised by muscle lesion associated with the mineralisation of large muscle groups or other organs, in the absence of an alternative cause for the calcification, such as toxic, enzootic or metabolic. Molecular and histopathological aspects of the disease are still poorly elucidated.
Objectives: To describe the epidemiological, pathological and molecular aspects of systemic calcinosis in a convenience sample of six horses submitted to necropsy in the Southern and Midwestern regions of Brazil.
Differential detoxification enzyme profiles in C-corn strain and R-rice strain of Spodoptera frugiperda by comparative genomic analysis: insights into host adaptation.
BMC Genomics
January 2025
Provincial Key Laboratory for Agricultural Pest Management of Mountainous Region, Institute of Entomology, Guizhou University, Guiyang, 550025, China.
Background: The fall armyworm (FAW) Spodoptera frugiperda, a highly invasive, polyphagous pest, poses a global agricultural threat. It has two strains, the C-corn and R-rice strains, each with distinct host preferences. This study compares detoxification enzyme gene families across these strains and related Spodoptera species to explore their adaptation to diverse host plant metabolites.
View Article and Find Full Text PDFAlantolactone mitigates the elevation of blood pressure in mice induced by angiotensin II by inhibiting calcium channel activation.
BMC Cardiovasc Disord
January 2025
Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, 116044, China.
Background: The dried root of Inula helenium L., known as Inulae Radix in Mongolian medicine, is a widely used heat-clearing plant drug within the Asteraceae family. Alantolactone (ATL), a compound derived from Inulae Radix, is a sesquiterpene lactone with a range of biological activities.
View Article and Find Full Text PDFOmega-3 Polyunsaturated Fatty Acids in Chronic Obstructive Pulmonary Disease Patients with COVID-19: A Review.
Curr Nutr Rep
January 2025
Mind-Body Interface Research Center (MBI-Lab), China Medical University Hospital, Taichung, Taiwan.
Purpose Of The Review: Mounting evidence indicates that individuals with chronic obstructive pulmonary disease (COPD) face a heightened risk of severe outcomes upon contracting coronavirus disease 2019 (COVID-19). Current medications for COVID-19 often carry side effects, necessitating alternative therapies with improved tolerance. This review explores the biological mechanisms rendering COPD patients more susceptible to severe COVID-19 and investigates the potential of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in mitigating the severity of COVID-19 in COPD patients.
View Article and Find Full Text PDFPrognostic Factors for Mortality in Maintenance Hemodialysis Patients Infected with SARS-CoV-2.
J Nippon Med Sch
January 2025
Department of Endocrinology, Metabolism and Nephrology, Graduate School of Medicine, Nippon Medical School.
Background: Maintenance hemodialysis patients are immunosuppressed, which increases their mortality risk if they contract coronavirus disease 2019 (COVID-19).
Methods: We studied data from 36 consecutive patients undergoing maintenance hemodialysis who were diagnosed as having COVID-19 from January 2020 to September 2023. Clinical data such as age and sex, laboratory data, radiological findings, modalities for blood purification therapy, and outcome at the time of discharge were collected from their hospital records.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!