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)

Capsaicin induced a contraction of isolated strips from the guinea-pig urinary bladder which was more evident in the dome than in the neck and inhibited contractions induced by field stimulation, particularly in the neck. Both responses exhibited prompt desensitization and were tetrodotoxin-resistant, suggesting a specific action on transmitter release from sensory nerve terminals. Indeed, the contractile response in the dome was prevented by a substance P antagonist while the inhibitory response in the neck was prevented by immunoblockade with anticalcitonin gene-related peptide (CGRP) serum. Substance P produced a contraction of the guinea-pig bladder, being about 5 times more potent in the dome than in the neck, while CGRP inhibited the evoked contractions, being about 8 times more potent in the neck than in the dome. Further, the maximal effect of CGRP in the neck was almost double that in the dome. Substance P- and CGRP-like immunoreactivity were detected in both the dome and the neck with no regional differences for each peptide. CGRP-like immunoreactivity was 6.3 and 7.9 times higher than substance P-like immunoreactivity in the dome and the neck, respectively. Exposure to capsaicin evoked release of both substance P- and CGRP-like immunoreactivity from the dome and the neck. Peak CGRP-like immunoreactivity released by capsaicin was 12.3 and 8 times greater than substance P-like immunoreactivity in the dome and the neck, respectively. For each peptide, no difference was found in peak release in the dome vs neck. Total substance P-like immunoreactivity released from the neck was 25% lower than that released from the dome. The ability of CGRP to stimulate accumulation of 3',5' cyclic adenosine monophosphate in membranes prepared from the bladder muscle was greater in preparations from the neck than from the dome. These findings indicate that postjunctional mechanisms (type and number of receptors for sensory neuropeptides, coupling with second messengers) are a major determinant of the type of motor responses consequent of the release of sensory neuropeptides from capsaicin-sensitive nerves.
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PMID:Regional differences in the motor response to capsaicin in the guinea-pig urinary bladder: relative role of pre- and postjunctional factors related to neuropeptide-containing sensory nerves. 246 49

Binding of [125I]Bolton-Hunter labelled substance P (BH-SP) and [125I]human alpha-calcitonin gene-related peptide (h alpha CGRP) to rat bladder tissue sections was characterized and the respective binding sites localized by light-microscopic autoradiography. BH-SP binding sites were localized to epithelium, blood vessels and smooth muscle while hCGRP binding sites were present only over the epithelium. These results suggest that the range of biological actions of substance P and calcitonin gene-related peptide, which may be co-released from the same afferent terminals, might be determined by the different distributions of their respective receptors.
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PMID:A comparison of the distribution of substance P and calcitonin gene-related peptide receptors in the rat bladder. 246 3

Calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) has been measured in various tissues of control rats and rats pretreated with systemic capsaicin, s.c. (50 mg/kg as newborns or as adults, 125 mg/kg as adults) and compared with the tissue level of substance P- and tachykinin-like immunoreactivities (SP-LI and TK-LI). The rank order of CGRP-LI concentration in various tissues was as follows: trigeminal ganglion greater than urinary bladder greater than ureter much greater than distal duodenum much greater than proximal duodenum much greater than skin (snout) greater than thymus = right atrium = vas deferens. A complete depletion of CGRP-LI following capsaicin treatment of both adult and newborn animals was observed in urinary bladder, ureter, atrium, vas deferens and skin. Capsaicin pretreatment of both adult and newborn rats reduced CGRP-LI in the duodenum by about 50%. CGRP-LI in trigeminal ganglion was reduced only in newborn animals, while it was not affected in the thymus. The CGRP-LI/SO-LI ratio varied in these tissues between 33.2 (urinary bladder) and 0.9 (proximal duodenum). A significant correlation was found between CGRP-LI and SP-LI or TK-LI in tissues where immunoreactivities were depleted by capsaicin, as well as in the urinary bladder of individual animals. The correlation between CGRP-LI with SP-LI and TK-LI upon treatment with capsaicin indicates that neurons containing SP and TK as well as CGRP, and neurons containing CGRP only, are affected in a similar manner by capsaicin.
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PMID:Distribution of calcitonin gene-related peptide-like immunoreactivity in various rat tissues: correlation with substance P and other tachykinins and sensitivity to capsaicin. 246 30

These experiments further define the organization of peptidergic pathways in the paravertebral sympathetic system of the bullfrog. Populations of axons and synaptic boutons in sympathetic ganglia 9 and 10 were found to express calcitonin gene-related peptide-like immunoreactivity (CGRP-IR) and substance P-like immunoreactivity (SP-IR). CGRP-IR is present in fibers that run through the ganglia and in boutons that make contact with almost half of the principal neurons. SP-IR is also present in fibers within the ganglia and in a rare class of synaptic boutons that are found on less than 1% of the principal neurons. Both forms of immunoreactivity are coexpressed in some nerve fibers and in the rare synaptic boutons that contain SP-IR. Neuropeptide Y-like immunoreactivity (NPY-IR), a marker for C-type postganglionic neurons, was used to identify the postsynaptic targets of boutons containing CGRP-IR and SP-IR. Ninety-five percent of the ganglion cells contacted by CGRP-IR boutons were negative for NPY-IR and are therefore likely to be B-type postganglionic neurons. Similarly, 100% of the ganglion cells contacted by boutons containing SP-IR were negative for NPY-IR. Lesions of the sympathetic chain demonstrated that synaptic boutons containing CGRP-IR arise from neurons whose axons enter the chain rostral to ganglion 7. Cutting the chain between ganglia 8 and 9 eliminates all preganglionic B and C inputs to ganglia 9 and 10. The destruction of the preganglionic C pathway by this lesion was verified by staining ganglia 9 and 10 for luteinizing hormone releasing hormone (LHRH). This lesion also eliminated boutons containing CGRP-IR and drastically reduced the number of ganglionic fibers that stained for CGRP-IR and SP-IR. By contrast, cutting the sympathetic chain between ganglia 6 and 7 spared LHRH-IR in the preganglionic C pathway but still eliminated the boutons that normally express CGRP-IR and reduced the amount of staining for SP-IR. CGRP-IR in the sympathetic ganglia arises from preganglionic and sensory neurons whereas ganglionic SP-IR is purely sensory in origin. In the spinal cord, the preganglionic B and C neurons that innervate ganglia 9 and 10 are located in different segments. In segments that contain preganglionic B cells, but not those that contain C cells, there were 243 +/- 37 (mean +/- SD) neurons in the intermediolateral cell column that express CGRP-IR. However, no cell bodies containing SP-IR were found in this region of the spinal cord.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Preganglionic and sensory origins of calcitonin gene-related peptide-like and substance P-like immunoreactivities in bullfrog sympathetic ganglia. 247 76

1. Bradykinin and capsaicin were compared for their ability to elicit functional effects and to release sensory neuropeptides from guinea-pig isolated perfused hearts. 2. Both bradykinin (10 microM) and capsaicin (1 microM) produced a marked increase in coronary flow, a large positive chronotropic effect and a significant reduction in contractile strength. These actions were associated with a marked release of substance P-like immunoreactivity (SP-LI) and calcitonin gene-related-like immunoreactivity (CGRP-LI). The percentage of the tissue content of SP-LI and CGRP-LI released by each agent was similar, although bradykinin was less effective than capsaicin. The ratio of SP-LI/CGRP-LI released by both agents was similar to that present in cardiac tissue. 3. Neuropeptide release could be evoked only once with capsaicin but at least four times with bradykinin. Also, functional responses to capsaicin underwent desensitization. After either in vitro or systemic capsaicin pretreatment, the release of SP-LI and CGRP-LI by bradykinin was reduced and the positive chronotropic effect of bradykinin was significantly reduced, while the increase in coronary flow and negative inotropic responses remained unchanged. 4. Pretreatment with indomethacin (10 microM) strongly antagonized the release of SP-LI and CGRP-LI by bradykinin and reduced the increase in heart rate. 5. These findings suggest that activation by bradykinin (probably through indirect mechanisms) of capsaicin-sensitive sensory nerves in the heart, leads to a local release of sensory neuropeptides. These neuropeptides, in turn, could participate in determining the complex functional effects of this kinin on cardiac performance.
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PMID:A comparison of bradykinin- and capsaicin-induced myocardial and coronary effects in isolated perfused heart of guinea-pig: involvement of substance P and calcitonin gene-related peptide release. 247 43

The discovery of new peptides that may or may not be members of existing peptide families is stimulating research in the field of gastrointestinal motility. Before their function in control of human motility can be predicted, both anatomic and functional pathways must be determined in a number of animal models. In many instances this has just begun. In other instances old concepts must be revised. This review examines the recent findings that motor actions attributable to VIP and by extension to its colocalized family member PHI may occur by turning off a tonic release that has held the muscle in a relaxed state. For the opioid family, some of the very complex actions are probably attributable to its action to inhibit the tonic release of VIP. For the tachykinin/neurokinin family, the focus is on the potential role as a sensory transmitter released antidromically from afferent capsaicin-sensitive nerve endings. In summarizing the actions of galanin, the reader is cautioned against any extrapolation to other species, because the actions and structure of the peptides have been found to be different in each species examined. CGRP, again a sensory transmitter found colocalized with substance P, tends to exert an opposite action on the smooth muscle from substance P (that of relaxation), and the interactions between these peptides may well prove to be important in gastrointestinal reflexes. The PP, PYY, and NPY family require much more study in gastrointestinal motor systems but appear to act as presynaptic inhibitory transmitters in a variety of local motor reflexes. One caveat from one who studies these systems is never to predict the action of a new or old peptide in your system of study, because the complexity of the system appears to determine the action expressed.
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PMID:Control of gastrointestinal motility by peptides: old peptides, new tricks--new peptides, old tricks. 247 97

An immunoperoxidase method was used to investigate and compare the distribution of neuropeptide-immunoreactive (ir) nerve fibers and neurofilament-ir fibers in chick carotid body. The vagus nerve and its branches were intensely immunoreactive with an antiserum against chick neurofilaments. The branches from the vagus and the recurrent laryngeal nerves anastomosed within the connective tissue encircling the carotid body, and then entered the organ to form a network of neurofilament-ir fibers. Immunoreactivities for CGRP, somatostatin, galanin, VIP and substance P were found in the carotid body; they were located within varicose fibers. Immunoreactivity for each peptide was discretely and characteristically distributed. Dense networks of varicose CGRP-ir nerve fibers were found throughout the carotid body in close proximity to clusters of carotid body cells and to blood vessels. Substance P-ir fibers were distributed similarly to CGRP-ir fibers. Somatostatin-ir fibers appeared as patches distributed around chief cells. Numerous galanin- and VIP-ir nerve fibers were observed in the connective tissue surrounding the carotid body, but they occurred in only moderate densities in the parenchyma.
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PMID:Distribution of CGRP-, somatostatin-, galanin-, VIP-, and substance P-immunoreactive nerve fibers in the chicken carotid body. 247 54

Little is known of the significance of perivascular peptides in hypertension. In this study we have investigated the circulating levels of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and substance P- like immunoreactivity (SP-LI) during and after treatment of severe hypertension. Seventeen patients with a mean blood pressure of 204/127 mmHg were included. Circulating levels of CGRP-LI and SP-LI in normotensive controls were 35 +/- 4 and 1.2 +/- 0.1 pmol/l, respectively. In the hypertensives CGRP-LI was significantly lower (22 +/- 3 pmol/l: P less than 0.05) while SP-LI did not differ (1.6 +/- 0.3 pmol/l) from the normotensives. After treatment the circulating level of CGRP-LI was still significantly lower (16 +/- 2 pmol/l: P less than 0.001) while SP-LI remained unchanged when compared with the controls. These observations suggest an involvement of vascular afferent nerves in the aetiology of hypertension in man.
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PMID:Reduced levels of calcitonin gene-related peptide (CGRP) but not substance P during and after treatment of severe hypertension in man. 247 45

We have followed the development of perivascular nerve fibres using antisera to substance P, calcitonin gene related peptide, neuropeptide Y and vasoactive intestinal polypeptide in the mesenteric vascular bed of developing Sprague-Dawley rats. The pattern and density of innervation appeared to be determined by one week of age. The pattern of innervation by SP- and CGRP-positive fibres was similar. The pattern of innervation by neuropeptide Y-containing fibres was distinct from that of SP and CGRP. The VIP-positive fibre plexus was sparse and irregular compared with the others examined. The density of innervation by all fibre types was highest in the jejunal arteries.
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PMID:The peptidergic innervation of the developing mesenteric vascular bed in the rat. 247 13

1. Bradykinin (1 nm-1 microM) produced a contraction of bladder strips excised from the dome of the guinea-pig urinary bladder, an effect which was greatly enhanced by removal of the mucosal layer or by thiorphan (10 microM). All subsequent experiments were performed in mucosa-free strips and in the presence of thiorphan. 2. In carbachol (5 microM)-contracted strips, bradykinin produced a concentration (1 nm-1 microM)-dependent transient relaxation. 3. Kallidin was slightly more potent than bradykinin in producing a contraction and a relaxation of the carbachol-induced tone. By contrast, [des-Arg9]-bradykinin, a selective B1 receptor agonist was barely effective up to 1 microM. 4. The contractile response to bradykinin was: (a) unaffected by either tetrodotoxin (1 microM), in vitro capsaicin desensitization (10 microM for 30 min) or apamin (0.1 microM); (b) antagonized by indomethacin (5 microM), the prostaglandin receptor antagonist SC-19220 (100 microM) or the B2 receptor antagonist [D-Arg0, Hyp3, Thi5,8, Phe7]-bradykinin (10 micron) and (c) almost abolished by nifedipine (1 microM). 5. The antagonism of the contractile response to bradykinin produced by indomethacin and SC-19220 was non-additive while that produced by indomethacin and the B2 receptor antagonist was additive. 6. The relaxant response to bradykinin was unaffected by tetrodotoxin, in vitro capsaicin desensitization or indomethacin but antagonized in a competitive manner by the B2 receptor antagonist. Further, this response was abolished by apamin (0.1 microM) but unaffected by glibenclamide (1 microM). 7. Bradykinin (10 microM) produced a consistent release of calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) but not substance P-LI from the guinea-pig bladder muscle. CGRP-LI release by bradykinin was greatly reduced in bladders exposed to indomethacin. [des-Arg9]-bradykinin (10 microM) was ineffective. 8. We conclude that: (a) bradykinin-induced contraction involves activation of both B2 receptors and prostanoid synthesis, via distinct mechanisms which act by inducing calcium influx via nifedipine-sensitive channels; (b) bradykinin-induced relaxation involves activation of B2 receptors and opening of apamin-sensitive potassium channels; (c) bradykinin stimulates sensory nerves in this tissue largely via prostanoid production.
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PMID:Multiple mechanisms in the motor responses of the guinea-pig isolated urinary bladder to bradykinin. 247 41


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