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)

beta-Amyloid (1-40) and (25-35) have been reported to be toxic to primary cultured neurons. beta-Amyloid (1-40) was also reported to induce neurodegeneration following intracerebral injection. We attempted to replicate and extend these findings by injecting both the full length amyloid peptide and the 25-35 fragment. beta 1-40 (3 nmol in 1 microliter) or beta 25-35 (20 nmol in 2 microliters) in a vehicle of 10% DMSO (3 and 10 mM concentration, respectively) induced tissue loss and neurodegeneration. We also attempted to prevent the amyloid-induced damage by coinjecting 200 nmol of Substance P. There was no obvious reduction in the size of the lesions. Other studies, however, have reported antagonism of amyloid toxicity with tachykinin agonists. Since beta-amyloid does not appear to bind to tachykinin receptors, there is some question as to the site of the putative interaction of these peptides and, therefore, the mechanism by which beta-amyloid induces tissue damage. Our own results and published cell culture toxicity studies suggest that aggregation of the peptide and physical displacement of tissue may be responsible for both the neuronal and tissue loss, although this hypothesis is not consistent with other published findings.
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PMID:Intracerebral beta-amyloid(25-35) produces tissue damage: is it neurotoxic? 128 Dec 89

We investigated the effect of the putative beta 3 agonist BRL 35135 on non-adrenergic non-cholinergic (NANC) contractions in guinea-pig bronchial strips. BRL 35135 (10(-9) to 10(-6) M) did not alter the baseline tension but reduced NANC contractions induced by electrical field stimulation (EFS) in a concentration-dependent fashion without having a significant effect on the contraction induced by substance P (10(-6) M). BRL 35135 (10(-6) M) also reduced the contraction induced by capsaicin (10(-7) M). Likewise, BRL 37344 (10(-9) to 10(-6) M) reduced NANC contractions induced by EFS in a concentration-dependent fashion. While BRL 37344 up to concentrations of 10(-8) M did not alter the contraction induced by SP (10(-6) M), BRL 37344 (10(-8) M) significantly inhibited NANC contractions induced by EFS and capsaicin (10(-7) M), (P less than 0.01). The inhibitory effect of BRL 35135 (10(-6) M) on NANC contractions induced by EFS was not significantly altered by the non-selective beta-adrenoceptor antagonists, propranolol and pindolol (P greater than 0.10), by the beta 1-selective antagonists, atenolol and metoprolol (P greater than 0.20) (10(-8) to 10(-6) M), or by the alpha-adrenoceptor antagonist, phentolamine (10(-7) to 10(-5) M) (P greater than 0.50). These results suggest that beta 3 agonists exert a prejunctional inhibitory action on NANC contractions.
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PMID:Evidence that an atypical beta-adrenoceptor mediates the prejunctional inhibition of non-adrenergic non-cholinergic contraction in guinea-pig bronchi. 132 25

Transforming growth factor beta (TGF beta) influences the growth and differentiation of a wide variety of nonneuronal cells (nnc) during embryogenesis and in response to wounding. In the present study TGF beta 1 and TGF beta 2 were examined for their neurotrophic actions on neonatal rat dorsal root ganglion (DRG) neurons with ganglionic nnc in dissociated cultures. TGF beta 1 and TGF beta 2 each increased both neuronal survival and levels of the peptide neurotransmitter substance P (SP) expressed per neuron as well as per culture. TGF beta 1 was maximally effective at a concentration of 40 pM, whereas TGF beta 2 was about 10-fold less potent. Survival effects promoted by simultaneous treatment with both factors were not additive. TGF beta 1 also changed the morphology and distribution of DRG nnc which resulted in clustering of DRG neurons on top of the nnc. Cotreatment of the cultures with two different anti-nerve growth factor (NGF) antibodies eliminated the neurotrophic effects of TGF beta 1. However, treatment with TGF beta 1 did not alter NGF mRNA expression in the cultures nor did it change the amount of NGF in the medium. Further, TGF beta 1 greatly enhanced survival effects and SP stimulation promoted by exogenous NGF at concentrations up to 100 ng/ml. The neurotrophic effects of TGF beta 1 were significantly attenuated by decreasing the proportion of the ganglionic nnc, suggesting a role for these cells in mediating TGF beta 1 action on the neurons. It is hypothesized that the neurotrophic activity of TGF beta depended upon the presence of molecules immunologically related to NGF and that the effects of TGF beta were synergistic with NGF. These observations suggest that TGF beta may play a role in the differentiation and regeneration of DRG neurons in vivo.
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PMID:Transforming growth factor beta has neurotrophic actions on sensory neurons in vitro and is synergistic with nerve growth factor. 137 11

The amyloid beta protein (ABP) has been shown to interact with the substance P (SP) receptor in a cell culture model that may mimic the pathogenesis of Alzheimer's disease. In the present study, however, 4 fragments of ABP (beta 1-42, beta 1-16, beta 17-28, and beta 25-35) failed to interact with SP-induced Ca2+ mobilization in SP receptor-expressing cultured cells. Therefore, the action of these ABP-related peptides in our cultured cells is unrelated to the SP receptor.
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PMID:Amyloid beta protein substituent peptides do not interact with the substance P receptor expressed in cultured cells. 166 16

An in vivo model for the simultaneous study of the motility of the gallbladder, sphincter of Oddi and duodenal wall in the anesthetized cat was developed. Changes in gallbladder volume were recorded as well as changes in the outflow from the sphincter of Oddi and from a vein graft inserted through the duodenal wall during perfusion at constant pressure. The distribution of three peptide hormones (substance P-SP, vasoactive intestinal peptide-VIP and cholecystokinin-CCK) within the feline extrahepatic biliary tree was studied immunocytochemically. Nerve terminals with SP-like immunoreactivity (LI) were distributed to the smooth muscle layers and also to acetylcholinesterase-positive ganglions cells in the intrinsic plexa. SP-LI was further demonstrated in cell bodies of the intrinsic plexa as well as in vagal axons. VIP-LI had a similar distribution. An especially rich VIP-ergic innervation was observed within the circular muscle layer of the sphincter of Oddi. SP-LI or VIP-LI did not occur in mucosal endocrine cells. On the other hand, CCK-LI was not demonstrated in nerves but occurred regularly in endocrine cells of the duodenal mucosa. Regional administration of SP elicited dose-dependent contractile motor effects on the biliary tree, which were not dependent on muscarinic or nicotinic cholinoceptors, but were inhibited by infusion of an antagonistic SP analogue indicating a direct effect on the smooth muscle cell. Efferent electrical vagal nerve stimulation elicited contractile motor responses, which were blocked by either atropine or infusion of the SP-analogue, indicating activation of a postganglionic cholinergic neuron via intrinsic or extrinsic SP neurons. These observation correlate well with the presence of SP nerve terminals on acetylcholinesterase-positive ganglion cells of the intrinsic plexa and SP axons within the vagus. An afferent mechanism cannot be excluded; antidromic activation of SP-containing axon collaterals from vagal afferents might act on intrinsic cholinergic neurons. The cellbodies of such afferents may be present in intrinsic plexa or within the sensory vagal nodose ganglion. VIP elicited relaxatory motor responses from the extrahepatic biliary tree, not influenced by blockade of cholinoceptors or beta-adrenoceptors. Stimulation of beta-adrenoceptors, or selective stimulation of beta 2-adrenoceptors caused dose-dependent relaxatory motor responses, which were antagonized by specific blockade. Stimulation of beta-adrenoceptors following selective blockade of beta 2-adrenoceptors resulted in relaxation, most probably mediated by beta 1-adrenoceptors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The vagal nerves and peptides in the control of extrahepatic biliary motility. An experimental study in the cat. 170 May 77

In atrial preparations obtained from reserpine-pre-treated guinea-pigs, incubated in the presence of 1 microM atropine plus 1 microM CGP 20712A (a beta 1 blocking drug), a positive inotropic effect due to CGRP release from capsaicin-sensitive sensory neurons was induced by electrical field stimulation (EFS). This response was concentration-dependently reduced by noradrenaline (0.01-3 microM), neuropeptide Y (NPY, 3-300 nM) and adenosine triphosphate (ATP, 1-30 microM). On the other hand, the overflow of [3H]-noradrenaline from sympathetic nerve terminals induced by EFS in isolated atria obtained from normal untreated animals was not modified in 10 nM calcitonin gene-related peptide (CGRP). Substance P (SP) and neurokinin A (NKA), at concentrations ranging from 0.01 to 1 microM did not affect the cardiac response to field stimulation of adrenergic terminals of atrial tissue. These findings demonstrate that all the co-transmitters stored in adrenergic nerve terminals have a modulatory role on the efferent function of cardiac capsaicin-sensitive sensory neurons, while cardiac adrenergic neurotransmission is not influenced by the peptidergic transmitters released from sensory neurons.
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PMID:Modulation by adrenergic transmitters of the efferent function of capsaicin-sensitive nerves in cardiac tissue. 172 21

We investigated the effect of sympathetic agonists, parasympathetic muscarinic agonists and substance P on depletion of secretory granules in acinar cells of rat von Ebner's gland. Drugs were injected intraperitoneally at several different concentrations. Antagonists were given 15 minutes before injection of the agonist, and the extent of depletion of secretory granules in glandular acini was calculated using a computerized color image analyzer. The specific alpha 2-sympathetic agonist clonidine and the beta 1-sympathetic agonist dobutamine produced a depletion of secretory granules. When combined with injections of the alpha 2-sympathetic antagonist yohimbine and the beta 1-sympathetic antagonist acebutolol, depletion of secretory granules was blocked. The parasympathetic muscarinic agonist carbachol also produced a depletion of secretory granules. QNB blocked the depletion caused by carbachol, while atropine partially inhibited depletion. The specific M1-muscarinic agonist McN-A-343 caused some depletion, although there was no significant differences between it and the control. Complete depletion of the secretory granules was achieved by carbachol stimulation superimposed on substance P stimulation. We concluded that the activation of the sympathetic alpha 2- and beta 1-receptors, as well as the M2 (M2 beta)-muscarinic and substance P receptors, results in degranulation of acinar cells in von Ebner's gland of the rat.
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PMID:Degranulation of acinar cells in von Ebner's gland of the rat. 172 93

1. Autoradiographic techniques have been used to examine the location of beta-adrenoceptors in the heart and beta-adrenoceptors, substance P receptors and muscarinic cholinoceptors in blood vessels. 2. Both beta 1-adrenoceptors and beta 2-adrenoceptors were present in guinea-pig and human heart, on the myocardium and associated with the cardiac nerves and blood vessels. 3. Nerves on the vasculature and vascular smooth muscle contained beta-adrenoceptors and muscarinic cholinoceptors. 4. Receptors for substance P and beta-adrenoceptors, but not muscarinic cholinoceptors were present on endothelial cells.
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PMID:Autoradiographic localization of receptors in the mammalian cardiovascular system. 244 8

In this study in conscious rats, we tested the hypothesis that substance P, a central pressor peptide and a potential transmitter substance of pain pathways, could be involved in the cardiovascular defense reaction that is typically associated with unpleasant sensory stimuli. The hemodynamic responses to centrally administered substance P were pharmacologically characterized. The increases in blood pressure and heart rate after intracerebroventricular injections of substance P were accompanied by mesenteric and renal vasoconstriction and hind limb vasodilation (pulsed-Doppler flow probes). The pressor and vasoconstrictor responses were attenuated by peripheral alpha 1-adrenoceptor blockade with prazosin but were not influenced by blockade of vascular vasopressin receptors with d(CH2)5Tyr(Me) arginine vasopressin (AVP). Cardiac beta 1-adrenoceptor blockade with metoprolol abolished the tachycardic and reduced the pressor responses. Substance P-induced hind limb vasodilation was not sensitive to intravenous atropine but was largely prevented by peripheral beta 2-adrenoceptor blockade with ICI 118,551. Thus, the substance P-induced pressor effects are mediated by alpha 1-adrenergic sympathetic vasoconstriction and beta 1-adrenergic cardiac stimulation, whereas the hind limb vasodilation is mainly due to beta 2-adrenergic stimulation. Substance P dose-dependently (0.01-10 micrograms i.c.v.) released oxytocin but not vasopressin or adrenocorticotropic hormone (ACTH) from the pituitary gland. High doses reduced basal ACTH levels. Together with the hemodynamic responses, a behavioral arousal reaction was observed, which included increased locomotion, grooming, scratching, and skin biting. Our results demonstrate that a neuropeptide can induce classic cardiovascular defense reaction.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Substance P induces a cardiovascular defense reaction in the rat: pharmacological characterization. 245 61

We investigated the role of neuropeptides and adrenergic agonists in the regulation of intracellular 3',5'-cyclic adenosine monophosphate (cyclic AMP) contents in cultured Schwann cells from sciatic nerve of neonatal Sprague-Dawley rats. Of the neuropeptides examined, vasoactive intestinal polypeptide (VIP) and secretin markedly stimulated the accumulation of intracellular cyclic AMP in a time- and dose-dependent manner with half maximum at 3 and 12 min, and 2.8 X 10(-5) and 5.0 X 10(-5) M, respectively. While somatostatin, substance P, adrenocorticotropin (ACTH), beta-endorphin, and nerve growth factor (NGF) did not show any effect on cyclic AMP metabolism, isoproterenol (IP), norepinephrine (NE) and epinephrine (E) also markedly elevated the Schwann cell cyclic AMP concentration. The rank-order of potency of these adrenergic catecholamines on cyclic AMP accumulation was isoproterenol greater than norepinephrine greater than epinephrine. Simultaneous addition of VIP or secretin to the Schwann cell culture synergistically enhanced the norepinephrine-induced elevation of intracellular cyclic AMP. The effect of norepinephrine was antagonized by a selective beta 1-adrenergic antagonist but not by beta 2- nor alpha-adrenergic antagonists. These results suggest that VIP, secretin, and beta 1-adrenergic agonists alone or synergistically may play a part in the regulation of metabolism of Schwann cells mediated through a cyclic AMP-dependent mechanism.
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PMID:Peptidergic and adrenergic regulation of the intracellular 3',5'-cyclic adenosine monophosphate content in cultured rat Schwann cells. 285 16


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