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)

To investigate the functional relationship between the enteric nervous system and the intestinal neurotensin (N) cells, the release of neurotensin (NT) was measured upon vascular 8-min infusion periods of various neurotransmitters and neuropeptides in an isolated vascularly perfused rat jejunoileum. NT-like immunoreactivity (NT-LI) was measured with an antiserum that specifically recognizes intact NT. The cholinergic agonists methacholine and carbachol produced a strong release of NT-LI (250% and 700% of basal, respectively at 10(-5) M). The infusion of a lower dose (10(-7) M) was less effective in both cases. The nicotinic receptor agonist DMPP (10(-4) M) had no significant effect on NT-LI release. Norepinephrine (10(-6) M) produced a moderate and well-sustained secretion of NT (200% of basal). Infusion of higher doses of these neurotransmitters dramatically increased the arterial pressure. G-amino-n-butyric acid (GABA), histamine, serotonin and dopamine administered at final concentrations up to 10(-5) M had no effect on NT-LI release. In contrast, gastrin-releasing peptide and bombesin induced a dose-dependent transient increase of portal NT-LI (maximal value at 10(-7) M: 1000% of basal) followed by a rapid return to near basal values. Substance P (10(-7) M) evoked a prompt release of NT-LI with a peak at 600% of basal followed by a decline to 200% of basal at the end of the session. Leu-enkephalin and calcitonin-gene-related-peptide (CGRP, 10(-7) M) produced a small rise in portal NT-LI, while Met-enkephalin, dynorphin, vasoactive intestinal peptide (VIP), galanin, neuropeptide Y (NPY), peptide histidine isoleucine (PHI), neuromedin U and thyrotropin releasing hormone (TRH) had no stimulatory effect. Our results indicate that additionally to the secretion of NT induced by cholinergic agents and bombesin, substance P and to a lesser extent Leu-enkephalin are capable of stimulating NT release in the rat.
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PMID:Release of ileal neurotensin in the rat by neurotransmitters and neuropeptides. 167 14

This light microscopic immunohistochemical study investigates the distribution and target interrelations of nerve fibers in bronchus-associated lymphoid tissues (BALT) of rat and cat by using antisera against (1) the polyneuronal marker protein gene product 9.5 (PGP 9.5), (2) selected opioid and nonopioid peptides, and (3) the marker enzymes tyrosine hydroxylase (TH) and dopamine beta-hydroxylase (DBH). In both species, a similar distribution pattern of PGP, peptide, and catecholamine enzyme immunoreactive was observed. Anti-PGP 9.5 stained all nerve fibers (except some smaller, calcitonin gene-related peptide-immunoreactive (CGRP-ir) fibers presumably of the C-type) throughout the different compartments of BALT, e.g., under the epithelium, in the smooth muscle layer, along the vasculature, and between immune cells of BALT parenchyma. The distribution of fibers staining for peptides (substance P (SP), (CGRP), neuropeptide Y (NPY). Leu-enkephalin, Met-enkephalin-Arg-Gly-Leu) and/or the catecholamine enzymes was also not compartment-specific. However, the density of the different peptidergic fibers and those staining for the marker enzymes exhibited region- and target-specific variations, e.g., fibers, cocontaining substance P and CGRP were more ubiquitous in nonvascular regions than codistributed NPY-, TH-, and DBH-ir fibers, which clearly prevailed in perivascular plexus. Regularly, nerve fibers staining for any of the peptides and markers investigated formed close contacts with mast cells, cells of the macrophage/monocyte cell line (identified as ED1 + cells), and/or other lymphoid cells, although with different frequencies. We assume that the SP/CGRP innervation is mainly of primary sensory origin, while the NPY innervation is chiefly derived from postganglionic noradrenergic sympathetic neurons. The VIP/PHI component is most likely postganglionic cholinergic while the opioid component, apparently derived from the Proenkephalin precursor, could be of differential origin. We propose that the neuroimmune connections in BALT play a significant role in the regulation and/or modulation of physiological/pathophysiological mechanisms of the lung. BALT may also be an integral part of the psycho-neuro-immune axis.
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PMID:The neuroimmune link in the bronchus-associated lymphoid tissue (BALT) of cat and rat: peptides and neural markers. 167 20

Substance P- and calcitonin gene-related peptide-like immunoreactivities (SP-LI and CGRP-LI, respectively) were measured in superfusates of either superior sagittal sinus and transverse sinuses and attached dura mater or dura mater alone of guinea pig. Exposure of cerebral venous sinuses to capsaicin (1 microM) evoked the release of both SP-LI and CGRP-LI, which was no longer observed upon second challenge with the drug. Neuropeptide release was induced by 80 mM K+ either at the first or second administration. Bradykinin (10 microM) increased the outflow of CGRP-LI, but not of SP-LI, from cerebral venous sinuses. In vitro capsaicin pretreatment (10 microM) or incubation with 10 microM indomethacin completely abolished the bradykinin-evoked CGRP-LI release. Capsaicin (1 microM) failed to evoke release from dura mater without major intracranial venous vessels. Sensory neuropeptide released from the cerebral venous sinuses may take part in certain symptoms, such as vasodilatation and inflammation accompanying the pain of the migraine attack. Bradykinin, putatively via prostanoid generation, may participate in this event.
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PMID:Release of sensory neuropeptides from dural venous sinuses of guinea pig. 169 Oct 44

1. Arteriolar diameter was measured using an optical method in preparations of guinea-pig submucosal plexus in vitro. Electrical stimulation of one or more neurones in ganglia of the submucosal plexus causes a cholinergic vasodilatation in normal animals. The vasomotor innervation to the arterioles was studied in guinea-pigs in which the extrinsic nerves to the intestine had been removed. Tissues were processed for immunohistochemistry after the in vitro experiments. 2. Extrinsic denervation resulted in complete loss of catecholamine fluorescence, NPY (neuropeptide Y) and CGRP (calcitonin gene-related peptide) immunofluorescence around the blood vessels and no neurogenic vasoconstriction was observed up to 60 days post-denervation. Vasodilatation in response to ganglionic stimulation was increased; smaller arterioles (outside diameter less than 40 microns) showed a greater enhancement of neurogenic vasodilatation than larger arterioles. 3. Nerve-evoked vasodilatations were only partially inhibited by muscarinic antagonists at 30-60 days after extrinsic denervations. 4. The non-cholinergic neurogenic vasodilatation was abolished by the substance P antagonists, spantide, [D-Arg1, D-Pro2, D-Trp7.9, Leu11]substance P and [D-Arg1, D-Phe5, D-Trp7.9, Leu11]substance P. These antagonists did not alter the cholinergic vasodilatation in normal or extrinsically denervated arterioles. 5. Exogenous substance P dilated all submucosal arterioles; the concentration which produced half-maximal vasodilatations was 2.5 mM in both normal and extrinsically denervated arterioles. Substance P antagonists inhibited the vasodilatation caused by substance P at concentrations similar to those needed to block nerve-mediated vasodilatation. 6. There was a strong correlation between the finding of non-cholinergic vasodilatation in response to ganglionic stimulation, and the presence of substance P-immunoreactive fibres running from ganglion to arteriole. This correlation did not exist for VIP (vasoactive intestinal peptide). 7. These results suggest that intrinsic intestinal substance P-containing nerve fibres supply submucosal arterioles after sympathetic efferents and sensory afferents are removed. Stimulation of these nerves releases substance P to produce arteriolar dilatation.
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PMID:Substance P mediates neurogenic vasodilatation in extrinsically denervated guinea-pig submucosal arterioles. 169 Dec 91

In the guinea pig isolated perfused lung, we have examined the relationship between the effects of capsaicin and neuropeptide release and the possible existence of an axon reflex arrangement. Bolus injections into the pulmonary artery of capsaicin (1-100 pmol), substance P (10-1,000 pmol), and neurokinin (NK) A (10-100 pmol) produced a concentration-dependent bronchoconstriction, whereas calcitonin gene-related peptide (CGRP, 20-40 nmol) was without effect. Repeated administration of capsaicin at 40- to 60-min intervals was not associated with tachyphylaxis. These data support the presence of a NK2- (or NKA) type of tachykinin receptor in the guinea pig airways. Tetrodotoxin (0.3-3 microM) inhibited the effect of capsaicin, indicating that an axon reflex was operant. Capsaicin increased overflow of CGRP-like immunoreactivity (-LI) and NKA-LI, the latter only during concurrent infusion of the enkephalinase inhibitor phosphoramidon (3 microM). Phosphoramidon also increased overflow of CGRP-LI, suggesting that both NKA and CGRP were catabolized by a similar enzyme. The purine nucleoside adenosine did not cause any detectable overflow of CGRP-LI, indicating that neuropeptides may not be involved in adenosine-evoked bronchoconstriction and that bronchoconstriction per se does not induce neuropeptide overflow. Capsaicin and NKA had only minor effects on buffer flow, whereas substance P produced pulmonary vasoconstriction. These data clearly demonstrate that capsaicin acts via an axon reflex in the guinea pig airways. Supramaximal concentrations of capsaicin are needed to detect neuropeptide overflow, but the possibility exists that released neuropeptides mediate its effects.
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PMID:Capsaicin-induced bronchoconstriction and neuropeptide release in guinea pig perfused lungs. 169 65

In addition to differences between the two submucosal ganglionic neural networks, i.e., the plexus submucosus externus (Schabadasch) and the plexus submucosus internus (Meissner), with respect to the occurrence and distribution of serotonin as neurotransmitter, immunocytochemistry also revealed a distinct distribution for various neuropeptides in these two plexuses. Immunoreactivity for galanin, vasoactive intestinal polypeptide, calcitonin gene-related peptide, substance P, neuromedin U, enkephalin, somatostatin and neuropeptide Y was found in varicose and non-varicose nerve fibres of both submucosal ganglionic plexuses, albeit with a distinct distributional pattern. The difference in neurotransmitter and/or neuromodulator content between both neural networks became even more obvious when attention was focussed on the immunoreactivity of the nerve cell bodies for these substances. Indeed, neuropeptide Y, enkephalin- and somatostatin-immunoreactive neuronal perikarya as well as serotonergic neuronal cell bodies appear solely in the plexus submucosus externus. Neuromedin U-immunoreactive perikarya, mostly coexisting with substance P, are observed in large numbers in the plexus submucosus internus, whilst they are rare in the plexus submucosus externus. Double-labelling immunostaining for substance P with CGRP and galanin revealed a different coexistence pattern for the two submucosal ganglionic plexuses. The differing chemical content of the neuronal populations supports the hypothesis that the existence of the two submucosal ganglionic plexuses, present in most large mammals including man, not only reflects a morphological difference but also points to differentiated functions.
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PMID:Distinct distribution of CGRP-, enkephalin-, galanin-, neuromedin U-, neuropeptide Y-, somatostatin-, substance P-, VIP- and serotonin-containing neurons in the two submucosal ganglionic neural networks of the porcine small intestine. 169 6

In the superfused isolated rat urinary bladder, capsaicin as well as electrical field stimulation evoked the release of calcitonin gene-related peptide-like immunoreactivity (CGRP-IR). Carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP, threshold 2 microM) reduced both, the capsaicin- and the electrical field stimulation-evoked release of CGRP-IR while a low concentration of Ruthenium Red (RR, 0.6 microM and 2 microM) selectively attenuated the capsaicin-evoked release of CGRP-IR but did not influence the effect of electrical field stimulation. 20 microM RR nearly abolished the capsaicin-evoked release, but also attenuated the effect of electrical field stimulation. In the isolated guinea-pig bronchus, electrical field stimulation and capsaicin induced non-cholinergic contractions which are known to be caused by tachykinin release from afferent nerve terminals. CCCP (0.6 microM) only reduced the response to field stimulation; a ten-fold higher concentration of CCCP attenuated field stimulation as well as capsaicin-induced contractions. This is in contrast to the reported selective inhibition of capsaicin-induced contractions by RR. The present data demonstrate that CCCP generally inhibits evoked neuropeptide release, regardless of the kind of stimulation used while low concentrations of RR preferentially inhibit capsaicin-evoked neuropeptide release.
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PMID:Effects of carbonyl cyanide p-trichloromethoxyphenylhydrazone (CCCP) and of ruthenium red (RR) on capsaicin-evoked neuropeptide release from peripheral terminals of primary afferent neurones. 169 4

The volume-evoked micturition reflex (VEMR) is under the control of a complex vesico-spino-bulbo-spino-vesical reflex arc. When functional this system provides for the storage and retention of urine and its subsequent efficient expulsion by virtue of a joint contraction of the bladder and synergic relaxation of the urethral sphincter. Transection of the spinal cord results in an initial disruption of this organization (areflexia) followed by a time-dependent change in the characteristics of the functioning of this reflex system. The growth of knowledge of the pharmacology of spinal systems has yielded considerable information on the potential spinal neurotransmitter systems and their associated receptors. Given the possible role of such systems in mediating and modulating the VEMR, a reasonable approach has been to investigate the effects of spinally administered agonists and antagonists in unanaesthetized animals in which the VEMR can be examined. Thus, it appears that the initial state of bladder distension is signalled by larger (A type) afferent fibres. After spinal injury and the loss of this supraspinal control, smaller unmyelinated C fibres play a predominant role in controlling this reflex. On stimulation these C fibres release peptides (VIP, CCK, substance P, CGRP) and excitatory amino acids (glutamate). Studies in this laboratory have shown that whereas administration of these peptides is without effect in normal intact rats, the antagonists for glutamate and VIP receptors (but not CCK) produce a dose-dependent increase in spontaneous bladder contractions with a corresponding decrease in the volume required to evoke a VEMR. Other spinal systems, such as those for opioids and GABA, are known to exert modulatory effects upon spinal somatomotor reflex arcs. In the spinal cord these agonists (mu/delta and GABAA/B) produce discrete changes in the VEMR in intact and spinally transected animals. Thus these studies may provide insight into the coordinated mechanisms which govern the VEMR and may also allow the development of pharmacological approaches to managing the dysfunctional bladder.
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PMID:The spinal pharmacology of urinary function: studies on urinary continence in the unanaesthetized rat. 169 10

Capsaicin (10(-9) to 10(-5) M) contracted guinea-pig tracheal strips. Epithelium-containing tracheal strips developed a maximum active tension which was significantly higher than that observed in epithelium-free strips. Anti-CGRP (calcitonin gene-related peptide) serum blocked the epithelium-dependent potentiation of the capsaicin-induced contraction in the intact tracheal strips, without affecting the response of the epithelium-free strips. This result suggests the occurrence of an epithelium-dependent release of CGRP. This same serum markedly reduced the contraction induced by exogenous rat CGRP in both intact and epithelium-free tracheal strips. In epithelium-free tracheal strips, capsaicin-induced contraction was abolished by spantide (10(-6) and 10(-5) M), a substance P antagonist, but, in intact tracheal strips, spantide did not abolish the capsaicin-induced contraction, showing that both CGRP and substance P release are directly induced by capsaicin. Moreover, the contractile responses to rat CGRP of intact tracheal strips from guinea pig suggest that CGRP itself might be able to release a contracting factor from the airway epithelium. Therefore, CGRP originating from the airway epithelium may play a major role in the control of airway smooth muscle tone.
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PMID:Evidence for the involvement of calcitonin gene-related peptide in the epithelium-dependent contraction of guinea-pig trachea in response to capsaicin. 170 Mar 8

Cryostat- and vibratome-cut rat kidney secretions were singly or doubly labeled to visualize immunoreactive calcitonin-gene-related peptide (CGRPI) and substance P (SPI). Rats were perfused with 2-4% paraformaldehyde + 0.15% picric acid then rinsed with buffer. Horseradish peroxidase (HRP) was used to visualize CGRP in vibratome sections, and combined HRP and fluorophore were used to visualize the two peptides simultaneously in cryostat sections. There is a complex, multilayered plexus of CGRP nerves on the renal pelvis and a less dense, single-layered plexus on the major branches of the renal artery and on interlobar arteries and veins. A few axons innervate finer branches of the arterial tree and other intrarenal structures. Results of double immunolabeling suggest that SPI axons comprise a subpopulation of the CGRP axon population in the rat kidney. There was no evidence for a separate population of SPI axons.
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PMID:Calcitonin gene-related peptide-immunoreactive nerves in the rat kidney. 170 58


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