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At least 19 recordsLinked to original sources
PubMed1985

Isolation and characterization of substance P, substance P 5-11, and substance K from two metastatic ileal carcinoids.

Using an antiserum directed at the COOH-terminus of tachykinins, we have examined postmortem tissue from two cases of metastatic ileal carcinoid for the presence of tachykinin-like immunoreactivity. The vast majority of the immunoreactive tachykinin-like material eluted from a Sephadex G-50 column as two peaks at positions corresponding to molecular weights of 1300 and 850. The 1300 dalton peak was resolved by reverse-phase-HPLC into two components which by Edman sequencing, amino acid analysis, and fast atom bombardment (FAB)-mass spectrometry criteria, were identified as substance P and substance K. The 850 dalton peak was also resolved on RP-HPLC into two peaks which were resistant to Edman degradation but from amino acid analysis and FAB-mass spectrometry criteria were identified as pyro-Glu-substance P 5-11 and oxidized pyro-Glu-substance P 5-11. In control experiments substance P 5-11 was converted to pyro-Glu-substance P 5-11 during the extraction procedure. Both tumors also contained a minor immunoreactive peak which eluted from a Sephadex G-50 sizing column at a position corresponding to a molecular weight of 4000 which probably represents neuropeptide K. These results suggest that beta-preprotachykinin is preferentially expressed in carcinoid tumors and that substance K may also play a role in the carcinoid syndrome.

Amino Acid Sequence↗
PubMed1992

[The potencies of substance P, substance P fragments, and compound 48/80 for granulocyte infiltration in mouse skin].

To determine whether the N-terminal or C-terminal peptide of substance P (SP) induces granulocyte infiltration in mouse skin, we examined the potencies of SP, the N-terminal peptides SP1-4 and SP1-9, the C-terminal peptides SP4-11 and SP6-11, and a mast cell degranulating agent compound 48/80 in inducing granulocyte (neutrophil and eosinophil) infiltration in the skin of BALB/c mice. The subcutaneous administration of SP (10(-7)-10(-5) M) caused granulocyte infiltration in mouse skin in a concentration-dependent fashion 6 h after the injection. SP1-9 (10(-5)-10(-4) M) also caused granulocyte infiltration in the skin which was associated with mast cell degranulation. However, SP1-4, SP4-11 and SP6-11 (up to 10(-4) M) induced neither granulocyte infiltration nor mast cell degranulation. In addition, compound 48/80 (0.5-50 micrograms/ml) also induced granulocyte infiltration of mouse skin with a concentration-dependent increase in mast cell degranulation. These results indicate that SP induces granulocyte infiltration of mouse skin through mast cell degranulation induced by the N-terminal peptide.

Animals↗
PubMed1986

Dopamine antagonist haloperidol decreases substance P, substance K, and preprotachykinin mRNAs in rat striatonigral neurons.

Rat genomic clones were used to quantitate preprotachykinin mRNAs in the rat basal ganglia, while the tachykinin peptide products substance P and substance K were measured by radioimmunoassay. Administration of the dopamine antagonist (antipsychotic) drug haloperidol significantly decreased substance P, substance K, and both alpha (substance P encoding) and beta (substance P/substance K encoding) preprotachykinin mRNAs, suggesting a drug-induced decrease in striatonigral tachykinin biosynthesis. The time course for decreased preprotachykinin mRNAs and tachykinins apparently parallels the period of maximum risk for the development of certain antipsychotic drug-induced extrapyramidal side effects seen clinically. Tachykinin interaction with dopamine neurons may play an important role in the modulation of basal ganglia function.

Animals↗
PubMed1986

Effects of substance P and substance P antagonists on rat salivary secretion.

The intra-arterial infusion of substance P produced dose-related responses of both parotid and submandibular salivary secretion in anesthetized rats. The substance P-induced secretion in both glands was inhibited by the substance P analogues [D-Arg1, D-Trp7.9, Leu11]-substance P and [D-Arg1, D-Pro2, D-Trp7.9, Leu11]-substance P, but not by [D-Pro2, D-Trp7,9]-substance P. The profiles of protein and calcium levels obtained with substance P-induced salivary secretion for both glands were similar to those produced by acetylcholine stimulation and were not altered by the substance P analogues.

Animals↗
PubMed1988

Receptor binding sites for substance P and substance K in the canine gastrointestinal tract and their possible role in inflammatory bowel disease.

The mammalian tachykinins, substance P, substance K (neurokinin A) and neuromedin K (neurokinin B), are putative peptide neurotransmitters in both the brain and peripheral tissues. We used quantitative receptor autoradiography to localize and quantify the distribution of binding sites for radiolabeled substance P, substance K and neuromedin K in the canine gastrointestinal tract. Substance P binding sites were localized to smooth muscle cells in the muscularis mucosa and muscularis externa, the smooth muscle and endothelium of arterioles and venules, neurons in the myenteric plexus, mucosal epithelial cells, exocrine cells and lymph nodules. Substance K binding sites were distributed in a pattern distinct from substance P binding sites and were localized to smooth muscle cells in the muscularis mucosa and muscularis externa, the smooth muscle and endothelium of arterioles and venules, and neurons of the myenteric plexus. Neuromedin K binding sites were not observed in any area of the canine gastrointestinal tract although they were localized with high specific/non-specific binding ratios in the canine spinal cord. These results indicate that there are at least two distinct types of tachykinin receptor binding sites in the canine gastrointestinal tract, one of which probably recognizes substance P and the other substance K as endogenous ligands. In correlation with previous physiological data, these substance P and substance K receptor binding sites appear to be involved in the regulation of a variety of gastrointestinal functions including gastric motility, mucosal ion transport, hemodynamics, digestive enzyme secretion and neuronal excitability. In addition these results demonstrate that receptor binding sites for substance P and substance K are expressed by cells involved in mediating inflammatory and immune responses. These data, together with our studies on surgical specimens from patients with inflammatory bowel disease, suggest that in a pathophysiological state tachykinins and their receptors may play a role in inflammatory bowel disease and should permit a rational approach to designing neuropeptide antagonists which may prove effective in treating inflammatory diseases.

Animals↗
PubMed1989

Influence of substance P and substance P--sequences on immunocompetent cells.

The influence of substance P (SP) and substance P-sequences on spleen cell cultures of mice and on rat lymph node mononuclear cells was studied. SP and the N-terminal fragments SP(1-4) and SP(1-7) were capable of inducing the secretion of lymphokines with chemotactic properties for polymorphonuclear leukocytes and lymphocytes. The peak of the dose-response curves appeared in a concentration range of 10(-11) to 10(-10) mol/l. The predominant migratory stimulatory activity was found at a molecular mass of 12,000 and 23,000 dalton and an inhibitory activity at 35,000 dalton. The C-terminal part of the peptide, SP(6-11), SP(7-11), SP(8-11), SP(9-11), was not able to induce such lymphokine secretion. The experimental results display the importance of the N-terminal fragment for the lymphokine secretion, and support the hypothesis that SP is also a peptide with modulatory functions in the immune response.

Animals↗
PubMed1988

Airway responses to substance P and substance P fragments in the guinea pig.

Airway responses to rapid intravenous infusions of substance P (SP), selected carboxy terminal fragments (SP3-11, SP5-11, SP7-11, and SP9-11), and an amino terminal fragment (SP1-9) were measured in anesthetized, mechanically ventilated guinea pigs. The dose of each peptide required to decrease pulmonary conductance (GL) to 50% of baseline value was calculated in each animal. The order of ED50GL was: SP5-11 less than SP3-11 less than SP less than SP7-11. SP9-11 and SP1-9 were inactive at doses up to 1000 nmol/kg i.v. The effects of the neutral metalloendopeptidase (NEP) inhibitor, thiorphan, and the angiotensin converting enzyme (ACE) inhibitor, captopril, on airway responses to SP5-11 were examined in order to test the hypothesis that differences in degradation of SP and SP5-11 contribute to the difference in airway responsiveness to the two peptides. Thiorphan (0.5 mg/animal, i.v.) caused a significant decrease in ED50GL for SP5-11, as has been previously noted for SP. In contrast, captopril (1.7 mg/animal i.v.) had no effect on ED50GL for SP5-11, although it has a substantial effect on SP responses. These results indicate that while the carboxy terminal of SP is essential for peptide bronchoactivity, loss of amino terminal peptides (up to four residues) actually enhances bronchoconstrictor responses to the peptide. Part of this enhancement appears to result from differences in the degradation of SP and SP5-11 by ACE. The data suggest that cleavage of SP by dipeptidyl aminopeptidases could enhance its bioactivity.

Amino Acid Sequence↗
PubMed1985

Effects of substance P and substance P-(6-11) on hormone release from isolated perfused pancreas: their opposite actions on rat and canine islets.

The effects of substance P (SP) and SP-(6-11) (SP6-11) on hormone secretion from the isolated perfused pancreas were compared in rats and dogs under the same conditions. In the rat, SP inhibited insulin secretion in a dose-dependent manner in a concentration range of 0.1-10 nM. Glucagon secretion was inhibited at a minimal dose of 10 nM SP. No significant effect on somatostatin secretion was obtained. SP6-11 exhibited the identical inhibitory potency as SP on both insulin and glucagon release from the rat pancreas. In the canine pancreas, by contrast, 1 and 10 nM SP and SP6-11, respectively, potentiated the release of insulin, glucagon, and somatostatin. Potentiation by SP6-11 was less than that by SP. These results demonstrate species differences in the effects of SP and SP6-11 on the release of pancreatic hormones.

Animals↗
PubMed1985

Characterization of the hyperalgesic effect induced by intrathecal injection of substance P.

Substance P (SP) was administered to awake rats by injection into the lumbar subarachnoid space via an indwelling cannula. Intrathecal (i.t.) injection of substance P produced a dose-related hyperalgesic response in the tail-pressure assay. This hyperalgesic effect peaked at 1 min and returned to control level within 15 min. Tachyphylaxis to the action of substance P was not observed by successive intrathecal injections. The hyperalgesic effect induced by substance P was increased by pretreatment with naloxone and blocked by a large dose of morphine. A synthetic analogue (D-Pro2, D-Trp7,9)-substance P, was not found to block the action of substance P on mechanical responses. These results suggest that substance P apparently produces a direct action on spinal substance P receptors and the antagonistic effect of morphine on the hyperalgesia induced by substance P may be mediated through a postsynaptic mechanism in the spinal cord.

Animals↗
PubMed1986

Regulation of surfactant secretion from isolated Type II pneumocytes by substance P.

Substance P, an eleven amino acid neuropeptide, significantly inhibited release of [3H]phosphatidylcholine from pulmonary Type II epithelial cells in vitro. Basal release and release in response to the beta-adrenergic agonist, terbutaline and 12-O-tetradecanoylphorbol 13-acetate (TPA) were significantly decreased in the presence of substance P. Inhibitory effects of substance P were noted following a 1 h exposure of primary cultures of Type II cells in vitro and persisted up to 3 h in the presence of the secretagogues, TPA and terbutaline. The IC50 values for substance P inhibition of [3H]PC release were 10 microM for basal release, 40 microM for TPA-induced release and 50 microM for terbutaline-induced release. The related neuropeptide, physalaemin and the stable active analog of substance P, [pGlu5, MePhe8, MeGly9]substance P [5-11], had no significant inhibitory effects on surfactant release whether in the presence or absence of TPA or terbutaline. These data support the hypothesis that NH2-terminal basic groups of substance P are necessary for inhibition of surfactant secretion from isolated Type II cells and support the concept that an inhibitory system contributes to mediation of surfactant secretion from Type II epithelial cells.

Animals↗
PubMed1986

The localization and characterization of substance P and substance K in striatonigral neurons.

Specific substance P and substance K radioimmunoassays coupled to high-performance liquid chromatography were used to characterize striatal and nigral tachykinin immunoreactivity. Using these assays, authentic substance P and substance K accounted for nearly all substance P and substance K immunoreactivity, respectively. A series of coronal knife cuts of the striatum caused parallel depletions in nigral substance P and substance K, consistent with the possible colocalization of these tachykinins in striatonigral neurons.

Animals↗
PubMed1985

Comparison of the effects of substance P and substance K on blood pressure, salivation and urinary bladder motility in urethane-anaesthetized rats.

The effects of substance P and substance K on blood pressure, salivation and urinary bladder motility were investigated in urethane-anaesthetized rats. On intravenous administration, both peptides produced dose-related reductions in blood pressure, substance P being 25-30 times more potent than substance K. Substance P induced a dose-dependent increase of salivation, while substance K was half as active and induced only 40% of the maximum effect of substance P. The two tachykinins induced contractions of the urinary bladder, substance K being about twice as effective as substance P. Substance K was more effective than substance P in activating micturition. These findings provide further evidence that multiple receptor types are involved in mediating the effects of tachykinins in peripheral organs.

Anesthesia↗
PubMed1985

Analysis of the mechanism of histamine release induced by substance P.

Substance P causes release of histamine from rat peritoneal mast cells; the structure-activity relationship shows that N-terminal residue is essential and the hydrophobic region of C-terminal plays an important role. Electrical conductivity of black lipid membrane containing phosphatidic acid was augmented by substance P. In this case, N-terminal residues and C-terminal hydrophobicity were also unavoidable. The partitioning of substance P into the organic phase increased in the presence of phosphatidic acid. The CD spectrum of substance P was changed from the unordered form to beta-form by coexistence of phosphatidic acid/PC liposomes in the medium. The addition of calcium or magnesium in the test solution is effective to prevent either of these phenomena. These findings indicate that substance P probably binds to negatively charged sites of membrane lipids, and subsequent penetration of C-terminal into the hydrophobic core of lipid bilayer may induce an increase of membrane permeability and the following histamine release.

Animals↗
PubMed1989

Effects of activators and antagonists of the neuropeptides substance P and substance K on cell proliferation in planarians.

Substance P and substance K (Neurokinin A) are mammalian peptides belonging to the tachykinin family. Both have been studied extensively, are widely distributed in both central and peripheral mammalian nervous systems, and seem to be involved in pain reactions and inflammatory responses. We report here that substance P and substance K, as well as Epidermal Growth Factor (EGF), are potent mitogens, at micro and nanomolar concentrations, for planarian cells. This stimulation is inhibited by the substance P and substance K antagonist spantide, while capsaicin, a pungent agent of capsicum peppers that destroys sensory neurons, stimulates cell division, probably through release of substance P. These results, jointly with the reported stimulation of cell division by naloxone and its inhibition by Met-Enkephalin (Baguña, 1986), both probably acting on tachykinin release, suggest that target cells, the neoblasts, must have in their cell membranes numerous receptors for growth hormones and neuropeptides analogous to their mammalian counterparts.

Animals↗
PubMedDate not supplied

Stimulation of connective tissue cell growth by substance P and substance K.

Connective tissue cells proliferate actively when cultured in the presence of serum. Platelet-derived growth factor (PDGF), a basic protein of relative molecular mass approximately 30,000, has been identified as the major serum mitogen for these cells; its main physiological/pathophysiological role may be to initiate wound healing in connection with tissue injury. However, growth of cultured cells is also influenced by several other factors, including epidermal growth factor, fibroblast growth factor, insulin and somatomedins. Furthermore, Rozengurt and Sinnett-Smith recently showed that bombesin, a neuroendocrine peptide isolated from frog skin, stimulates DNA synthesis and cell division in cultures of a specific subtype of 3T3 cells. Substance P and substance K (also known as neurokinin A or neuromedin L) are mammalian peptides belonging to the tachykinin family. Substance P has been studied extensively; it is distributed widely throughout the central and peripheral nervous system, including primary sensory neurones, and can be released in the periphery from axon collaterals of stimulated pain fibres and contribute to the inflammatory response. Substance K is a member of the tachykinin family isolated from mammalian spinal cord; Nawa et al. determined the primary structure of two types of substance P precursors, one of which contained a sequence homologous to substance K, as well as the sequence of substance P. We report here that substance P and substance K stimulate DNA synthesis in cultured arterial smooth muscle cells and human skin fibroblasts, and that this stimulation is inhibited by the substance P-antagonist spantide.

Animals↗
PubMed1989

Differential modulation of Ca2(+)-activated K+ channels by substance P.

Substance P released from motoneurons or primary afferent nerves innervating the gut is an excitatory noncholinergic regulator of gastrointestinal motility and has been shown to stimulate contractions in longitudinal colonic muscle. By using the patch-clamp technique on single myocytes from the longitudinal muscle of the rabbit colon, we have studied the action of the peptide on membrane conductances. In cell-attached patches, addition of the peptide to the bath activates a large conductance Ca2(+)-activated K+ channel. At peptide concentrations (10(-12) M) that did not result in cell contraction, K+ channels were activated in a synchronized, cyclical fashion. The activation did not occur in the presence of nifedipine (10(-6) M), a blocker of dihydropyridine-sensitive Ca2+ channels. The activation was also absent when the cells were depolarized in 126 mM KCl-Ringer solution. In contrast, at a concentration of the peptide (10(-7) M) that resulted in cell contraction, there was a transient activation of K+ channels, followed by a prolonged inhibition. Nifedipine (10(-6) M) did not block the K+ channel activation by this concentration of the peptide. Removal of bath Ca2+ abolished activation of the K+ channels by both the high and low concentrations of substance P. These results indicate that substance P exerts its effect via two different membrane pathways for extracellular Ca2+.

Animals↗
PubMed1988

Effects of substance P and substance K on the growth of cultured keratinocytes.

The effects of substance P and substance K, which are coexpressed in the same mRNA as a beta-preprotachykinin in peripheral tissues and released in the inflammatory lesion of the skin, were examined on epidermal proliferation using spontaneously transformed mouse epidermal cell line (Pam 212 cells). Substance P stimulated the synthesis of DNA of Pam 212 cells in the medium containing 2%-10% fetal calf serum (FCS). Stimulation of DNA synthesis was dose dependent if the cells were cultured in the medium containing 2% FCS (quiescent condition). This effect was inhibited by spantide. In a serum-free medium, substance P had no effect on keratinocyte proliferation. In contrast, substance K, which shares a common amino acid sequence with substance P on its C-terminal, did not affect DNA synthesis of Pam 212 cells in either medium condition. Substance P released in inflammation may stimulate epidermal proliferation.

Animals↗