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)

Electrical field stimulation (5 Hz) evoked a prompt outflow of calcitonin gene-related peptide- and substance P-like immunoreactivities (CGRP-LI and SP-LI, respectively) from superfused slices of the dorsal but not ventral half of the rat spinal cord. The evoked outflow was abolished by tetrodotoxin, calcium-free medium or previous exposure to capsaicin, indicating that it is produced through action potentials invading the central terminals of capsaicin-sensitive primary afferents. Adenosine as well as gamma-aminobutyric acid (GABA) or the GABAB receptor agonist (-)-baclofen produced a concentration-dependent inhibition of the evoked CGRP-LI outflow. Adenosine also inhibited the evoked SP-LI outflow. These findings demonstrate that inhibition of transmitter release from primary afferent neurons should be considered as a possible mechanism of the antinociceptive action of adenosine and adenosine analogs.
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PMID:Adenosine inhibits action potential-dependent release of calcitonin gene-related peptide- and substance P-like immunoreactivities from primary afferents in rat spinal cord. 127 86

Slices of human iris or ciliary body, obtained post-mortem (8-12 h after death, n = 5), were superfused in vitro with capsaicin (10 microM) and the immunoreactivity for substance P (SP-LI) or calcitonin gene-related peptide (CGRP-LI) was measured in the effluent. In the iris and in the ciliary body CGRP-LI was 3.71 +/- 0.74 pmol/g and 3.01 +/- 0.55 pmol/g and SP-LI was 6.68 +/- 0.75 pmol/g and 6.55 +/- 0.84 pmol/g, respectively. A first exposure to capsaicin increased the CGRP-LI outflow from the ciliary body (427 +/- 46 fmol/g/30 min), whereas a second challenge with the drug 30 min later, failed to significantly enhance the CGRP-LI outflow (21.8 +/- 15.6 fmol/g/30 min). Likewise, the capsaicin-evoked increase in CGRP-LI outflow from the iris slices (472 +/- 62 fmol/g/30 min) was no longer observed at the second drug administration (38.4 +/- 12.8 fmol/g/30 min). Capsaicin failed to increase the SP-LI outflow from either the iris or the ciliary body. Reverse phase HPLC analysis of CGRP-LI indicated that authentic CGRP was contained in the tissue and in the superfusate collected during exposure to capsaicin. The present results show that in the human iris and ciliary body, capsaicin releases CGRP possibly contained in terminals of sensory nerves.
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PMID:Capsaicin releases calcitonin gene-related peptide from the human iris and ciliary body in vitro. 128 Aug 43

The recurrent laryngeal nerve (RLN) consists of various motor, sensory and autonomic nerve fibers, although it has not been established whether different neuronal types exhibit a similar ability to regenerate. To address this question, freezing was used to injure the cat RLN fibers and the presence or absence of immunoreactivity for neuropeptides or transmitter-synthesizing enzymes was then examined as a marker to classify the fibers. In the control RLN, calcitonin gene-related peptide-immunoreactive (CGRP-IR) fibers were the highest in number and were distributed throughout the nerve fascicles. The number of substance P-immunoreactive (SP-IR) fibers was about 40% that of CGRP-IR fibers, while a portion of CGRP-IR fibers was found to contain SP immunoreactivity. Relatively low numbers of tyrosine hydroxylase-immunoreactive (TH-IR) and neuropeptide Y (NPY-IR) nerve fibers were seen which tended to form clusters. The distribution pattern of NPY-IR fibers was very similar to that of TH-IR fibers. In the regenerating RLN 1 week after the freezing injury, the fastest growing axons were CGRP-IR, while the regenerating rates of SP-IR, TH-IR and NPY-IR fibers were slower than that of CGRP-IR fibers. These results suggest that the ability for neurite regeneration varies among neuron types and that CGRP-IR fibers possess the most rapid ability to regenerate.
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PMID:Neurite regeneration in the cat recurrent laryngeal nerve: an immunohistochemical study. 128 3

To determine if intrathecal (i.t.) oxymetazoline (OXY) induces histological evidence of spinal neurotoxicity, male, Sprague-Dawley rats (300-450 g; implanted with an i.t. catheter) were treated with i.t. saline or 100 nmol OXY twice daily for 3 days, or 200 or 300 nmol OXY once daily for 3 days. Spantide (D-Arg1, D-Try7,9, Leu11-substance P; 0.067 nmol = 0.1 microgram, 0.167 nmol = 0.25 microgram or 0.334 nmol = 0.5 microgram) or capsaicin (0.164 mumol = 50 micrograms), given as a single i.t. injection, were used as positive controls. Animals were killed 12 h after the last injection of saline or OXY, and 72 h after spantide or capsaicin. Spinal cord sections (L1 and adjacent segments) were examined by light microscopy for changes in gross morphology, substance P-like immunoreactivity (SP-IR) and calcitonin gene related peptide-like immunoreactivity (CGRP-IR). All doses of i.t. OXY produced antinociception (tail-flick ED50 = 53.7 nmol, paw pressure withdrawal ED50 = 93.3 nmol). Rectal temperature decreased by 1.5-2.4 degrees C up to 12 h after 100 nmol of i.t. OXY. There were no signs of inflammation or necrosis, and no detectable loss or damage to either spinal afferents or motor neurons as judged by SP-IR and CGRP-IR structures in spinal cords of OXY-treated animals (all doses) as compared to i.t. saline controls. Spantide (0.1 microgram) had no antinociceptive or neurotoxic effect; 0.25 microgram induced irreversible loss of the TF reflex and transient hind limb paralysis; 0.5 microgram induced irreversible loss of TF and PP responses, permanent hind limb paralysis, bladder and bowel dysfunction. The spinal cords from these animals showed signs of extensive necrosis, cavitation, and haemorrhage in the ventral horn accompanied by a loss of CGRP-IR motor neurons. Capsaicin-treated rats exhibited a permanent loss of the TF but not the PP response and a marked reduction of SP-IR spinal afferents in the dorsal horn. It is concluded that i.t. OXY produces antinociception in the rat with no detectable spinal neurotoxicity as assessed by parameters which are sensitive to the neurotoxins, spantide and capsaicin.
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PMID:Intrathecal oxymetazoline does not produce neurotoxicity in the spinal cord of the rat. 128 63

Although pulpal neuropeptides such as calcitonin gene-related peptide and substance P may mediate neurogenic inflammation, little is known about the regulation of neuropeptide release from dental pulp. This article describes an in vitro method for superfusing dental pulp which permits the study of mechanisms regulating the release of immunoreactive CGRP (iCGRP). Tissue extracts from bovine dental pulp dilute in parallel to authentic calcitonin gene-related peptide and substance P peptide standards when assayed by radioimmunoassay. Pulpal levels of iCGRP were 17-fold greater than levels of immunoreactive substance P. Administration of a potassium pulse evoked a significant release of iCGRP from dental pulp (155 +/- 21 fmol/g/9 min) as compared with iCGRP spontaneously released from concurrent control chambers (18 +/- 11 fmol/g/9 min). The in vitro superfusion of pulp tissue may serve as a useful method for identifying peripherally acting drugs which modulate nociceptor secretory activity and for determining their mechanisms of action.
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PMID:An in vitro method to evaluate regulation of neuropeptide release from dental pulp. 128 48

Light and electronmicroscopic data reveal the presence of a well developed nerve plexus in the gut of the earthworm. The plexus contains subepithelial solitary nerve cells and fibers and an extensive neuropil among the muscle cells. There are two types of nerve cells in the enteric plexus. The first type contains mainly dense-core vesicles, and exhibits glyoxylic-acid induced fluorescence. Since none of these cells showed serotonin immunoreactivity, they are probably noradrenergic or dopaminergic. The second type contains large dense granules, suggesting that these cells are peptidergic (neurosecretory). A part of these cells are substance P immunoreactive, however no NPY, CGRP, or proctolin immunopositive cells were found. Ultrastructurally seven types of nerve fibers can be distinguished in the neuropil. Their distribution shows great variability within parts of the enteric canal. The observation that only two types of nerve cells are located within the gut makes it probable that some of the axons are extrinsic. According to immunohistological studies they may come from the stomatogastric system or from the segmental nerves. This is further supported by the fact that there is a well-developed subepithelial serotoninergic plexus in the fore-gut. Two types of neuromuscular junctions can be visualized in the muscular layer. The first type, representing a phylogenetically earlier form, exhibits wide junctional gap and pre- or postjunctional membrane thickening. The second type is the close contact. There are significantly more junctions observed in the fore-gut than in other parts of the gut.
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PMID:Immunohistochemical and ultrastructural study of the enteric nervous system of earthworm, Lumbricus terrestris L. 128 60

In patients with severe hypertension and in age and sex matched controls the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P-LI were measured. Samples were taken before medication, after 2-4 weeks and 2-12 months of pharmacological treatment to normotension. In the control group CGRP-LI levels were significantly higher for females than for males. No such relation was seen for substance P-LI. There were no correlations between CGRP-LI, substance P-LI or blood pressure. In the untreated acute hypertensive group there was a significant correlation between circulating levels of CGRP-LI and both diastolic and systolic blood pressure. No such relationship was seen for substance P-LI. The plasma levels of substance P-LI were significantly elevated (2.8 +/- 4.0) compared to controls (1.3 +/- 1.3, pmol/l, mean +/- S.D., p < 0.01). The levels of CGRP-LI did not differ from the control group. After 2-4 weeks of treatment the blood pressure decreased significantly and the plasma levels of substance P-LI were normalized while the CGRP-LI still did not differ from that of controls. After 2-12 months of treatment the blood pressure was still normalized, and the plasma levels of CGRP-LI and substance P-LI were not different from the control group. In the present study there was a positive correlation in hypertensives between the circulating CGRP-LI levels and diastolic and systolic blood pressure and elevated levels of substance P-LI. This would implicate the existence of a dynamic control through which the sensory system may register and damp the pressure response.
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PMID:Sensory nerve terminal activity in severe hypertension as reflected by circulating calcitonin gene-related peptide (CGRP) and substance P. 128 70

Peptide mediators or neuropeptides released from sensory nerves may induce inflammatory effects in airways, but their effects on airway blood velocity and lung resistance have not been previously studied simultaneously in awake animals. Nine adult sheep were chronically prepared for continuous measurement of blood flow velocity to the distal trachea and bronchi by surgical implantation of a 20-MHz pulsed Doppler flow probe on the common bronchial branch of the bronchoesophageal artery. Awake restrained animals were intubated and connected to a pneumotachograph to measure resistance to airflow across the lung (RL). Doubling doses of bradykinin (BK, 0.02-1.51 nmol/kg), calcitonin gene-related peptide (CGRP, 0.004-0.26 nmol/kg), or substance P (SP, 0.02-1.19 nmol/kg) were injected as a bolus into the right atrium while mean arterial pressure (MAP), bronchial blood velocity (Vbr), and RL were measured. BK at 0.76 nmol/kg caused a transient dose-related increase in Vbr from a baseline of 19.3 +/- 2.5 to 41.4 +/- 4.1 (SE) cm/s (P less than 0.05) despite a decrease in MAP from 118 +/- 6 to 80 +/- 6 mmHg. CGRP at 0.26 nmol/kg caused a transient dose-related increase in Vbr from 16.8 +/- 2.7 to 25.3 +/- 4.7 cm/s (P less than 0.05) despite a decrease in MAP from 113 +/- 5 to 87 +/- 8 mmHg. Neither BK nor CGRP affected RL. SP at 1.19 nmol/kg transiently increased Vbr from 18.3 +/- 2.3 to 45.1 +/- 8.3 cm/s (P less than 0.05), MAP from 138 +/- 9 to 162 +/- 15 mmHg, and RL from 4.5 +/- 1.0 to 106.6 +/- 62.1 cmH2O.l-1.s.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Peptide mediator effects on bronchial blood velocity and lung resistance in conscious sheep. 137 12

The distribution of perikarya showing substance P- (SP) or calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) in the rat trigeminal ganglion (TG) were investigated by means of immunohistochemical methods. Approximately 50% of the perikarya contain CGRP while SP-LI was observed in 1/3 of the cells. IR fibres were seen to leave the ganglion via the ophthalmic, maxillary, and mandibular nerves. The combination of peptide histochemistry and retrograde labelling of cells in the ganglion following injection of a fluorescent tracer into the pineal gland reveals that few SP- or CGRP-LI trigeminal neurons innervate the pineal gland. In contrast, the vast majority of perikarya in the TG were labelled upon application of the tracer to the meningeal surface supporting the view that meninges and meningeal arteries in rodents are heavily innervated by SP- and CGRP-LI trigeminal neurons.
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PMID:Substance P- and calcitonin gene-related peptide-like immunoreactive neurons in the rat trigeminal ganglion--with special reference to meningeal and pineal innervation. 137 81

Neuropeptides, synthesized in dorsal root ganglia (DRG), are implicated in nociception and neurogenic inflammation. Alterations in DRG neuropeptide levels have been described in polyarthritic rats, but these models are associated with widespread systemic disease. Using mild adjuvant-mediated monoarthritis of the left carpal joint we found significant increases in substance P (+69%) and calcitonin gene-related peptide (CGRP; +204+), but not somatostatin in ipsilateral C6/7 DRG. Peptide levels in contralateral DRG and other ipsilateral DRG were unaltered. Substance P and CGRP in DRG may be of importance in the pathogenesis and maintenance of adjuvant arthritis.
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PMID:Increase in substance P and CGRP, but not somatostatin content of innervating dorsal root ganglia in adjuvant monoarthritis in the rat. 137 70


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