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)

Bombesin, substance P and several structurally related peptides cause excessive grooming behavior after intracerebroventricular injection in mice. The present study describes the behavioral characteristics of these effects after acute administration. Substance P caused an elevation of grooming behavior which was short-lasting (less than 15 minutes), while bombesin induced both grooming and scratching behavior with a duration of action of about 2.5 hours. After repeated injections of high doses of either bombesin or a metabolically stable substance P analog, no tolerance-formation to these peptide-induced effects could be observed. Morphine partially antagonized bombesin-induced behaviors at a dose of 7.5 mg/kg subcutaneously while the same dose did not attentuate substance P-induced grooming. These results suggest that the behavioral changes induced by substance P and bombesin are mediated by distinct mechanisms. The lack of tolerance formation, together with the partial antagonism by morphine, suggests that the bombesin-induced behaviors may be related to a stimulation of nociceptive mechanisms.
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PMID:Behavioral alterations induced by substance P, bombesin, and related peptides in mice. 242 88

Digestion of human foreskin with collagenase and hyaluronidase disperses approximately 3.4 X 10(7) nucleated cells per gram of tissue, of which mast cells constitute 4.7%. These may be purified to 80% by use of density gradient centrifugation. The majority of mast cells (79%) measured between 9 and 13 micron in diameter, and the mean histamine content was 4.6 pg/cell. Viability was demonstrated by trypan blue exclusion by 93% of the cells and the low spontaneous histamine secretion of less than 7% in functional studies. Anti-IgE released up to 17.5% of cell-associated histamine within 5 to 7 min. Calcium ionophore-induced release was optimal with 0.3 microM A23187 when 28.6% histamine was released. Unlike human lung mast cells, skin mast cells released histamine in response to compound 48/80 and poly-L-lysine. This release, which was complete within 20 sec, was totally dependent on intact glycolysis and oxidative phosphorylation and partially dependent on extracellular calcium. The same characteristics were observed with secretion induced by substance P and morphine. The weak activity of eledoisin and physalaemin suggests that the substance P receptor, like that of the rat mast cell, is not of the classical types described for smooth muscle. Morphine-induced secretion was partially blocked by naloxone in a manner not compatible with competitive antagonism at a classical opioid receptor. The sensitivity of skin mast cells to nonimmunologic stimulation clearly distinguishes them from mast cells of the lung and lymphoid tissues and provides evidence of functional heterogeneity within human mast cells.
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PMID:Human skin mast cells: their dispersion, purification, and secretory characterization. 243 32

The effects of three tachykinins [substance P (SP), physalaemin (PH), and eledoisin-related peptide (ERP)] were investigated in anesthetized paralyzed guinea pigs. We measured airway resistance (R) and dynamic thoracic elastance (E) with a computerized technique, and blood pressure via a carotid artery. Tachykinins injected iv or intra-aortically (ia) induced dose-dependent increases in R and E, 4 times greater on iv than ia injection. They did not give rise to tachyphylaxis. As a bronchoconstrictor, PH was 5.0X and ERP 1.8X more potent than SP; time to peak response was longer for PH than for ERP and SP; and hypotensive responses, which were of similar magnitude for all three substances, lasted longest after PH. Bronchoconstrictor responses were unaltered by bilateral vagotomy, atropine, mecamylamine, and mepyramine. Morphine reduced PH-induced increases in R (P less than 0.01) and E (P less than 0.05), which were not reversed by naloxone, and capsaicin treatment 1 week before the experiments reduced both SP- and PH-induced increases in E (P less than 0.05). [D-Pro2,D-Trp7,9]-SP reduced ERP-induced increases in R and E, and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP reduced both SP- and PH-induced increases in R and E. We conclude that PH is the most potent bronchoconstrictor of the tachykinins tested. Tachykinin-induced bronchospasm is 'non-reflex' arising via a direct effect on airway smooth muscle; the release of histamine, acetylcholine, or other tachykinins is not involved in the responses. [D-Pro2,D-Trp7,9]-SP is more effective at SP-E receptors, and [D-Arg1,D-Pro2,D-Trp7,9,Leu11]-SP at SP-P receptors; both types of receptor are located all along the airways.
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PMID:Comparison of the bronchoconstrictor and cardiovascular effects of some tachykinins in guinea pigs. 243 17

To further examine the role that substance P plays in initiating the observed massive postmortem bronchoconstriction in guinea pig lungs and to explore the role of neural reflex in this airway spasm, six groups of animals were employed: control (n = 6), morphine (n = 6), substance P (n = 5), chronic capsaicin pretreatment + substance P (n = 5), tetrodotoxin (TTX) + acute capsaicin (n = 4), and chlorisondamine + acute capsaicin (n = 5). Pressure-volume curves were performed prior to and following the initiation of artificial pulmonary perfusion with 1% bovine serum albumin and 5% dextran in Tyrode's solution. A decrease in inflation volume (the lung volume between transpulmonary pressure of 0 and 30 cmH2O during inflation) was used as an index of bronchoconstriction. In control animals, inflation volume decreased to 20-30% of the base-line value at 15-30 min of perfusion, indicating massive bronchial constriction during this time period. Morphine (an agent inhibiting substance P release) significantly attenuated the spasm, whereas the presence of substance P in the perfusate markedly enhanced the constriction. Depletion of endogenous substance P by chronic capsaicin pretreatment did not affect exogenous substance P-induced spasm. Acute capsaicin-induced bronchoconstriction was significantly attenuated by TTX but was not affected by the ganglionic blocking agent, chlorisondamine. These data suggest that substance P initiates the massive postmortem bronchoconstriction in guinea pig lungs and that substance P is released by local stimulation of sensory nerve endings via axonal reflex.
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PMID:Substance P-inducing massive postmortem bronchoconstriction in guinea pig lungs. 243 99

A role of opioids as inhibitors of the non-adrenergic non-cholinergic (NANC) excitatory nerves has been studied in the guinea-pig bronchi using electrical field stimulation. Morphine and DAGO gave dose-dependent inhibition of NANC contraction, which was reversed by naloxone, whereas the cholinergic nerve and substance P responses were unaffected. [Met5]enkephalin and [Leu5]enkephalin weakly inhibited NANC contraction, whereas dynorphin-(1-13) had no effect. These results suggest that opiates inhibit NANC bronchoconstriction via mu-opioid receptors.
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PMID:Mu-opioid receptors modulate non-cholinergic constrictor nerves in guinea-pig airways. 244 46

Opioid drugs have been shown to inhibit neurogenic plasma exudation in skin by a presynaptic mechanism. We determined whether a similar inhibitory effect operates in the airways of anesthetized guinea pigs in vivo with the use of Evans blue dye as a marker of plasma leakage. Stimulation of the vagus nerve significantly increased leakage of dye in trachea and main bronchi (by approximately 300 and 600%, respectively). Similar increases in leakage were seen in the presence of atropine and propranolol. Morphine (1-30 mg/kg iv) inhibited leakage in a dose-related manner with complete inhibition in the trachea at a dose of 30 mg/kg. The inhibition was blocked by the opioid receptor-antagonist naloxone (1 mg/kg iv). Intravenous substance P significantly increased leakage but was not inhibited by morphine. We conclude that morphine inhibits neurogenic plasma leakage by presynaptic inhibition of release of neuropeptides from sensory nerve endings. If similar mechanisms are operative in human airways, inhibition of neurogenic plasma leakage by opioid drugs devoid of central effects may be of value in the therapy of asthma.
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PMID:Neurogenic plasma extravasation: inhibition by morphine in guinea pig airways in vivo. 246 90

Substance P (SP) has been proposed as a mediator of nociception in the dorsal horn of the spinal cord. Activation of nociceptive pathways by stimuli such as formalin injected into the hind paw has been shown to produce an increase in the amount of immunoreactive SP in primary afferent neurons. Opiate agonist and antagonist binding in the dorsal horn has been shown to affect the SP levels and release. In order to determine the effects of opiates on SP mediated nociception in the spinal cord, anesthetized rats pretreated subcutaneously with morphine, naloxone, or saline were injected in the right hind paw with 0.4 ml of either saline of 5% formalin. After 1 h, the animals were perfused and the lumbar enlargement of the spinal cord removed. SP-like immunoreactivity (SPLI) in the dorsal horns was quantitated using immunohistochemical staining and manual photometry. The results show that formalin injection increases the SPLI in the dorsal horn after 1 h, as does pretreatment with morphine. Morphine pretreatment combined with formalin injection further increases SPLI, but not significantly higher than either treatment alone. The morphine-induced increases could be blocked by naloxone, which had no effects on saline-treated controls. Most importantly, naloxone was able to block the formalin-induced increase in SPLI, implying that endogenous opioid systems play a role in the SP increases seen during formalin-induced nociception.
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PMID:Naloxone blocks the formalin-induced increase of substance P in the dorsal horn. 247 46

Previous investigations find that morphine administered i.c.v. induces antinociception directly at supraspinal sites and indirectly via activation of descending spinal systems. Independent experimentation suggests substance P and N-methyl-D-aspartate (NMDA) administered intrathecally (i.t.) can act as putative pain neurotransmitters to stimulate afferent pathways mediating nociception. The present studies were designed to determine whether a functional link exists between these observations. Mice were administered morphine i.c.v. 15 min before i.t. injections of substance P or NMDA. Additional investigations utilized coadministration of substance P or NMDA i.t. with one of several antagonists. Morphine administered i.c.v. inhibited both substance P- and NMDA-induced behavior in a dose-dependent manner. Coadministration of noradrenergic or adenosine receptor antagonists with substance P or NMDA i.t. dose-dependently reversed morphine (i.c.v.)-mediated inhibition. Methysergide injected i.t. caused significant, but only partially effective, antagonism of the effects of morphine (i.c.v.). Naloxone coadministered i.t. was effective in reversing morphine (i.c.v.)-mediated inhibition of NMDA-induced behavior, but ineffective in the substance P assay. These data demonstrate a functional link between activation of descending systems mediating antinociception by morphine (i.c.v.) and inhibition of putative pain neurotransmitters by spinally active antinociceptive agents. The potential involvement of serotonergic and opioid spinal systems is not clear, but noradrenergic and adenosine spinal pathways appear to play an important role in the indirect actions of morphine (i.c.v.). Differences in the inhibition of NMDA- and substance P-induced behavior also provide evidence for the presence of substance P and NMDA receptors in separate afferent pathways transmitting nociceptive stimuli.
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PMID:Morphine (intracerebroventricular) activates spinal systems to inhibit behavior induced by putative pain neurotransmitters. 248 Oct 30

The mechanism of the blood pressure (BP)-lowering effect of neurotensin (NT) in the anesthetized, ganglion-blocked guinea pigs was further examined using animals in which the basal BP was artificially raised by an IV infusion of noradrenaline (NA) to overcome the BP-lowering effect of the anesthesia as well as of the ganglion blocker. The animals were also vagotomized and given atropine at the beginning of the experiments to prevent potential baroreceptor-mediated vagal reflexes and/or activation of muscarinic receptors by endogenous acetylcholine. Under these experimental conditions, the IV bolus injections of NT as well as of capsaicin (a reference drug) produced dose-dependent hypotensive effects and variable levels of tachycardia. Omitting the ganglion blocker from the animal drug regimen attenuated but did not abolish the BP-lowering effect of NT and of capsaicin. Neither the hypotensive nor the tachycardic effects of NT and of capsaicin in ganglion-blocked guinea pigs were affected by prior animal treatment with propranolol (a beta adrenoceptor blocker), antihistaminics (mepyramine, cimetidine) or indomethacin (a cyclooxygenase inhibitor). Morphine was found to slightly reduced the hypotensive effect of NT without altering its slight tachycardic effect. Both the hypotensive and tachycardic effects of NT and of capsaicin, in contrast to those elicited by substance P (SP) and calcitonin gene-related peptide (CGRP), were inhibited in ganglion-blocked guinea pigs pretreated four days previously with capsaicin.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Capsaicin-sensitive primary afferents are involved in the hypotensive effect of neurotensin in ganglion-blocked guinea pigs. 248 46

Capsaicin has been shown to evoke the release of substance P (SP) from small diameter primary afferent fibers. Using an in vivo perfusion of the rat spinal cord, this study examined the pharmacology of opioid receptor systems which modulate the capsaicin-evoked release of SP. The addition of capsaicin (200 microM) to the perfusate raised SP-like immunoreactivity (SP-LI) from resting levels of 31 +/- 5 to 74 +/- 14 pg/ml or an increase of 139% above the baseline. Using high pressure liquid chromatography (HPLC) the identity of the released SP-LI was determined to coelute primarily with authentic SP or the oxidized form of SP. Opioid receptor agonists were added to the perfusate and their ability to inhibit capsaicin-evoked release of SP-LI was assessed. Morphine (10-100 microM), DAGO (1-100 microM), DPLPE (10-100 microM), but not U50488H (100 microM) produced a dose-dependent reduction in the capsaicin-evoked release of SP-LI. Pretreatment with the opioid receptor antagonist naloxone (1 mg/kg, IP) had no effect on the basal or capsaicin-evoked release of SP-LI. Naloxone pretreatment was able to antagonize completely the opioid-produced inhibition of capsaicin-evoked SP-LI release. These data indicate that the release of SP from primary afferent fibers can be modulated by the activation of mu or delta but not kappa opioid receptors. Further, these data support the hypothesis that spinally administered mu and delta opioid agonists may produce their antinociceptive effect through the presynaptic inhibition of neuropeptide release from small diameter primary afferent fibers.
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PMID:Opioid modulation of capsaicin-evoked release of substance P from rat spinal cord in vivo. 248 63


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