The role of substance P in neural reflex pathways activated by stroking was investigated in muscle-stripped segments of distal colon from guinea pigs. Stroking the mucosal surface with a brush at 1 stroke/s evoked an increase in short-circuit current (Isc) indicative of chloride secretion. The response to mucosal stroking was maximally reduced by 69-75% by the antagonist GR-82334. The agonist [Sar9,Met(O2)11] substance P caused a bumetanide-sensitive increase in Isc when added to the mucosal or serosal bath. Ablation of extrinsic afferents with acute or chronic administration of capsaicin did not alter the mucosal stroking response. Reverse transcription-polymerase chain reaction and in situ hybridization revealed the presence of neurokinin1 (NK1) receptor messenger RNA in isolated colonocytes or crypt glands. Ligand binding of 125I-Bolton-Hunter-labeled substance P was inhibited by GR-82334. The 50% inhibitory concentration was 0.84 nM. The results demonstrate a role for substance P released from capsaicin-insensitive submucosal neurons and in mucosal stroking reflexes. The presence of NK1 receptors on isolated colonocytes suggests that appropriate elements are present for axon reflex activation of intestinal epithelial cells.
These findings highlight families at risk for treatment abandonment, underlying reasons, and opportunities to improve retention in care for pediatric cancer patients in SSA.
SUMMARYVariations in the general protein and 40 enzymes of the 8 European pathotypes of the potato cyst nematode Globodera rostochiensis and G. pallida have been examined by isoelectric focusing (IEF) and cluster analysis. Differences in the protein patterns were observed and the presence of a major band at pH 8·0 allowed the two species to be discriminated. Extra isozymed of peptidase (EC 3.4. 11.*) and esterase (EC 3. 1. 1. 1) were also found in G. rostochiensis. Intra-species variation was seen within G. rostochiensis for superoxide dismutase (EC 1. 15. 1. 1) and within G. pallida for phosphoglucomutase (EC 2. 7. 5. 1) and glucose phosphate isomerase (EC 5. 3. 1. 9). The results suggest that the two species are very similar and the prospect for recognizing their pathotypes by IEF is discussed.
Reverse transcription--polymerase chain reaction of mRNA from rat RBL-2H3 cells yielded a 316 base pair band consistent with that predicted for the neurokinin-1 (NK1) receptor. Saturation and competition binding with 125I-labeled Bolton-Hunter substance P, substance P fragments, and a series of selective tachykinin receptor agonists and antagonists demonstrated that RBL-2H3 cells express high affinity binding sites for substance P on their surfaces with the kinetic and pharmacological properties of NK1 receptors. The pharmacology of these 125I-labeled substance P binding sites was (from most to least potent) [Sar9,Met(O2)11]substance P > substance P 4-11 >> GR82334 << MEN 10,376. However, substance P 1-4, substance P 8-11, substance P 9-11, and [Trp7, beta-Ala8]neurokinin A 4-10 failed to compete for binding. The metabolically stable NK1 receptor agonist, [Sar9,Met(O2)11] substance P, caused a 49% increase in 5-hydroxytryptamine release above basal levels. The results demonstrate the presence of functional NK1 receptors on RBL-2H3 cells, a mucosal-like mast cell line.
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