Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A capsaicin test involving peripheral nociception, which produces behaviour similar to that elicited by formalin, is described in mice. Capsaicin was injected subcutaneously (s.c.) into the dorsal surface of a hindpaw and the time the animals spent licking the paw was recorded. Doses of capsaicin of 6.25-1600 ng induced nociception, during a period of 5 min, starting immediately after injection and disappearing completely at 10 min. Intrathecally (i.t.) administered [D-Arg1,D-Trp7,9,Leu11]substance P (spantide), a tachykinin antagonist and [D-Phe7,D-His9]substance P (6-11), a selective antagonist of substance P (SP), inhibited the capsaicin-induced behaviour, in a dose-dependent manner. This licking behaviour was also inhibited by intrathecal administration of SP antiserum but not by somatostatin (SOM) antiserum. Intrathecal pretreatment with capsaicin resulted in a marked reduction of the licking response, following subcutaneous injection of capsaicin into the paw. Capsaicin-induced licking was not affected by intrathecal administration of cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-(OBz)-Thr], a SOM antagonist and by intrathecal pretreatment with cysteamine, a SOM depletor. This nociceptive test may allow discrimination between SP- and SOM-mediated responses in the spinal cord of the mouse.
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PMID:The capsaicin test in mice for evaluating tachykinin antagonists in the spinal cord. 128 12

An extract of the whole brain of the alligator (Alligator mississipiensis) contained very high concentrations of substance P-like immunoreactivity (405 pmol/g wet tissue) and neurokinin A-like immunoreactivity (514 pmol/g), as measured with antisera raised against the mammalian peptides. The primary structure of alligator substance P was established as: Arg-Pro-Arg-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2. This sequence is the same as that of chicken substance P and shows one substitution (Arg for Lys3) as compared with mammalian substance P. The neurokinin A-like immunoreactivity was separated into two components. Neuropeptide gamma was the most abundant peptide and its primary structure was established as Asp-Ala-Gly-Tyr-Gly-Gln-Ile-Ser-His-Lys-Arg-His-Lys-Thr-Asp-Ser- Phe-Val-Gly-Leu-Met-NH2. This sequence shows one substitution (Tyr for His4) compared with mammalian neuropeptide gamma. The second component was identical to mammalian neurokinin A. A peptide with the chromatographic properties of mammalian neuropeptide K was not identified in the extract.
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PMID:Structural characterization of tachykinins (neuropeptide gamma, neurokinin A, and substance P) from a reptile, Alligator mississipiensis. 128 82

A tachykinin peptide was isolated from an extract of the intestine of the European green frog, Rana ridibunda, and its primary structure was established as: His-Lys-Leu-Asp-Ser-Phe-Ile-Gly-Leu-Met.CONH2. This sequence was confirmed by chemical synthesis and shows two amino acid substitutions (leucine for threonine at position 3 and isoleucine for valine at position 7) compared with neurokinin A. Binding parameters for synthetic [Leu3,Ile7]neurokinin A and mammalian tachykinins were compared using receptor-selective radioligands and crude membranes from tissues enriched in the NK1, NK2 and NK3 receptors. [Leu3,Ile7]Neurokinin A was approx. 3-fold less potent than substance P in inhibiting the binding of 125I-labelled [Sar9,Met(O2)11]substance P (labelled with Bolton-Hunter reagent) to rat submandibular gland (NK1 receptor), 8-fold less potent than neurokinin A in inhibiting the binding of [2-[125I]iodohistidine1]neurokinin A to rat stomach fundus (NK2 receptor) and 6-fold less potent than neurokinin B in inhibiting the binding of 125I-Bolton-Hunter-labelled scyliorhinin II to rat brain (NK3 receptor). Thus the frog neurokinin A-related peptide shows moderate affinity but lack of selectivity for all three tachykinin-binding sites in rat tissues. This non-selectivity is similar to that displayed by the molluscan tachykinin, eledoisin, which also contains an isoleucine residue in the corresponding position in the molecule.
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PMID:Primary structure and receptor-binding properties of a neurokinin A-related peptide from frog gut. 133 83

This study describes the synthesis and effects of the first antagonist to the widely distributed neuropeptide, galanin, which inhibits the secretion of insulin. The first galanin antagonist is a 20-amino acid-long chimeric peptide of the composition galanin-(1-12)-Pro-substance P-(5-11) amide: Gly-Trp-Thr-Leu-Asn-Ser-Ala-Gly-Tyr-Leu-Leu-Gly-Pro-Gln-Gln-Phe-Phe-Gly- Leu-Met amide. The peptide dose dependently (IC50 = 1.0 nM) antagonizes the galanin-mediated inhibition of the glucose-induced insulin secretion from mouse pancreatic islets. The antagonist was also found to displace 125I-monoiodo-[Tyr26]galanin from membranes of the insulin producing Rin m 5F cells with an IC50 value of less than 0.1 nM. The antagonist is named galantide.
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PMID:The novel high-affinity antagonist, galantide, blocks the galanin-mediated inhibition of glucose-induced insulin secretion. 137 72

We investigated the affinity of several tachykinin antagonists reportedly selective for NK1 receptors at various tachykinin receptors and NK2 receptors subtypes. The four antagonists tested were: L 668,169, Spantide II, Ac-Thr-DTrp(for)-Phe-NMeBzl (FR 113680) and the novel nonpeptide antagonist (+/-)-CP-96,345. The four antagonists were found to be effective against NK1 receptor-mediated responses in the guinea-pig ileum with the following rank order of potency (pKB values in parentheses): (+/-)-CP-96,345 (8.11) greater than Spantide II (7.08) greater than FR 113680 (6.61) greater than or equal to L 558,169 (6.44). (+/-)-CP-96,345, Spantide II and FR 113680 were distinctly more potent at NK1 receptors than at NK2 receptors (NK2A in the rabbit pulmonary artery, NK2B in the hamster trachea). L 668,169 antagonized neurokinin A-induced contractions in the hamster trachea with an affinity similar (pKB value 6.16) to that found in the guinea-pig ileum for NK1 receptors (pKB value 6.44). All antagonists were inactive at NK3 receptors of the rat portal vein. In a second series of experiments, the affinities of test antagonists for NK1 receptors in the guinea-pig ileum were compared to those for NK1 receptors in the guinea-pig vas deferens, the rabbit jugular vein and the rat urinary bladder. For each antagonist, the affinity measured in the guinea-pig vas deferens and the rabbit jugular vein was comparable to that found in the guinea-pig ileum. In the rat urinary bladder, (+/-)-CP-96,345 was about 100 times less potent in blocking NK1 receptor-mediated contractions than in the guinea-pig ileum.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Activity of peptide and non-peptide antagonists at peripheral NK1 receptors. 138 19

Nociceptive response induced by 0.5% Formalin in the hindpaw of mice had two peaks, 0-5 min (first phase) and 15-20 min (second phase). By using the distinct biphasic response, the nature of the transmitter systems activated by Formalin in the spinal cord was studied for the purpose of determining the difference of the role of substance P (SP) and somatostatin (SST). The injection of (D-Pro2, D-Trp7,9)SP, (D-Arg1, D-Pro2, D-Trp7,9, Leu11)SP and SP antiserum inhibited only the first phase response. The i.t. injection of -Aminoheptanoyl-Phe-D-Trp-Lys-(OBz)-Thr- (an SST antagonist), SST antiserum and cysteamine (an SST depletor) inhibited only the second phase. This result indicates that SP is involved in the transmission of the first phase, and SST is involved in the transmission of the second phase of the Formalin-induced nociceptive response. With regard to other nociceptive stimuli, two i.t. SP antagonists produced a significant analgesia in the hot plate and tail pinch tests but had no effect in the acetic acid writhing test. However, i.t. SST antagonist and cysteamine produced a significant analgesia in the writhing test but had no effect in the hot plate and tail pinch test. These results suggest that SP participates in the transient pain induced by such acute stimuli as hot plate, tail pinch and the first phase of Formalin response and that SST participates in the prolonged and inflammatory pain induced by stimuli such as acetic acid and the second phase response.
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PMID:Roles of substance P and somatostatin on transmission of nociceptive information induced by formalin in spinal cord. 169 Aug 1

The effects of dorsal root stimulation and of substance P (SP), neurokinin A (NKA), and calcitonin gene-related peptide (CGRP) on the basal release of 9 endogenous amino acids, including glutamate (Glu) and aspartate (Asp), have been investigated using the rat spinal cord slice-dorsal root ganglion preparation and high-performance liquid chromatography with fluorimetric detection. High-intensity repetitive electrical stimulation of a lumbar dorsal root produced a Ca2(+)-dependent increase in the basal release of Asp, Glu, glycine (Gly), serine (Ser), and threonine (Thr). Low concentrations of SP (2 x 10(-7) M) caused a selective increase in the rate of basal release of Glu, whereas higher concentrations (1-5 x 10(-6) M) produced, in addition, an increase in the basal release of Asp. The SP-induced increase of Glu persisted in the absence of external Ca2+, but the effect was blocked by (D-Arg1, D-Pro2, D-Trp7,9, Leu11)-SP, an SP analog claimed to be an antagonist of the synthetic SP. NKA (5 x 10(-7) - 10(-6) M), a related tachykinin coexpressed with SP in primary sensory neurons, enhanced the basal release of Gly. CGRP (10(-7) M) caused a significant, largely Ca2(+)-independent increase in the basal release of Glu and Asp and a decrease in asparagine. SP and CGRP potentiated the electrically evoked release of Glu and Asp. Neonatal capsaicin treatment did not significantly alter the basal efflux of 9 endogenous amino acids from the spinal slices, but it prevented the dorsal root stimulation-evoked release of Asp, Glu, Gly, and Thr and the SP-induced increase in the basal release of Glu. However, the effect of CGRP was not significantly modified by the capsaicin treatment. These results indicate that tachykinins (SP and NKA) and CGRP are capable of modulating the basal and electrically evoked release of endogenous Glu and Asp, and these actions may provide an important mechanism by which the peptides contribute to the regulation of the primary afferent synaptic transmission. The enhancement of the basal and the dorsal root stimulation-evoked release of Glu and Asp by tachykinins and CGRP may have important physiological implications for strengthening the synaptic connections in the spinal dorsal horn.
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PMID:Tachykinins and calcitonin gene-related peptide enhance release of endogenous glutamate and aspartate from the rat spinal dorsal horn slice. 169 54

Somatostatin-14 (SS-14) and somatostatin-28 (SS-28) produce concentration dependent reductions in short-circuit current in rat colonic mucosa. EC50 values of 15.0 and 13.3 nM were obtained for SS-14 and SS-28 respectively while the N-terminal fragments of SS-28, namely somatostatin-(1-12) (SS1-12) and somatostatin-(1-14) (SS1-14) were inactive. Cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) and cyclo(Pro-Tyr-D-Trp-Lys-Thr-Phe) were potent antisecretory peptides, like SS-14 and SS-28; while the putative somatostatin antagonist, cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[Bzl]) exhibited neither agonist nor antagonist effects. Responses to SS-14 could be regulated by agents which affected the secretory state of the epithelium. Antisecretory effects of SS-14 were markedly attenuated by piroxicam and were restored following piroxicam plus either forskolin or vasoactive intestinal polypeptide (VIP). SS-14 also attenuated secretory responses produced by carbachol, substance P (SP), VIP and alpha- and beta-calcitonin gene related peptide (alpha-, beta-CGRP). Therefore, SS-14 exhibits broad spectrum antisecretory effects in rat descending colon mucosa.
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PMID:The antisecretory effects of somatostatin and analogues in rat descending colon mucosa. 170 67

The N-terminal tetrapeptide of substance P (SP1-4) was found to produce analgesia, after the icv injection to the rat brain, which is lower in its intensity than that produced by tuftsin (Thr-Lys-Pro-Arg tetrapeptide). Among investigated tuftsin analogues Thr-Lys-Pro-Thr and Thr-Lys-Pro-Thr-Asp (partial sequences of S-protein of HB virus) were weakly active, Thr-Arg-Pro-Arg was inactive, and Thr-Lys-Pro-Gly-Arg produced a weak hyperalgesia 30 min after the icv injection. The obtained results were compared with those obtained previously in the phagocytosis stimulation test. In the control experiments the effects of free amino acids of the tuftsin molecule (Thr, Lys, Pro, Arg) were also studied.
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PMID:Antinociceptive action of the SP1-4 tetrapeptide and of some tuftsin analogs. 171 Nov 98

Although numerous data support the existence of a presynaptic inhibitory control by opioids of substance P-containing primary afferent fibres entering the dorsal horn of the spinal cord, the exact nature of the opioid receptor involved in this control is still a matter of debate. In the present study, the potential role of delta opioid receptors was investigated by looking for the possible effects of selective delta ligands on the in vivo release of substance P-like material from the whole spinal cord in halothane-anaesthetized rats. Perfusion of the intrathecal space allowed the collection of substance P-like material that was released at a constant rate of approximately 0.65 pg substance P equivalents/min for at least 135 min. The addition of Tyr-D-Thr-Gly-Phe-Leu-Thr (10 microM) or dermenkephalin (10 microM), two selective delta agonists, to the perfusing fluid produced a marked reduction (-50-65%) in substance P-like material outflow which could be prevented by the selective delta antagonist naltrindole (10 microM) but not by naloxone (10 microM), which acts preferentially on mu opioid receptors. Furthermore, naltrindole alone (or the association of this antagonist plus dermenkephalin) enhanced the outflow of substance P-like material (+ 170%) as expected from the blockade of a tonic inhibitory control due to the stimulation of delta receptors by endogenous opioids.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:In vivo tonic inhibition of spinal substance P (-like material) release by endogenous opioid(s) acting at delta receptors. 172 87


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