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)

A broad mixture of inflammatory mediators ("inflammatory soup") was used to investigate the responsiveness of primary afferents from rat hairy skin in an in vitro skin-saphenous nerve preparation. In addition, a conditioning effect of the tachykinin substance P on chemosensitivity of nociceptors was examined. Inflammatory soup (IS) was made up in synthetic interstitial fluid from bradykinin, serotonin, histamin and prostaglandin E2 (all 10(-5) M). In addition, the potassium and the hydrogen ion concentration (7 mM, pH 7.0) and the temperature (39.5 degrees C) were elevated. The latter agents, in a control solution, did not excite nociceptors (n = 5). IS was repeatedly superfused over the receptive fields for 5 min at 10 min intervals; substance P (SP 10(-6) and 10(-5) M) was applied during the last 5 min of the interval and during the subsequent IS stimulation. IS excited more than 80% of the mechano-heat sensitive ("polymodal") afferents with slowly conducting nerve fibres (n = 72), but none of the low-threshold mechanoreceptive slow and fast conducting units (n = 17). Slow conducting afferents with high mechanical threshold (n = 35) were weakly, and less frequently (< 20%), driven by IS. A majority, but not all, of the responsive units showed tachyphylaxis upon repeated IS application. None, however, lost its responsiveness completely. Conditioning heat stimulation (32-46.5 degrees C in 20 s) did not enhance the subsequent IS response, which may indicate that sensitizing substances normally released by a noxious heat stimulus were already contained in IS. No sensitization to mechanical (von Frey) or heat stimulation could be established in the period after the IS response had subsided and after the washout was completed, respectively. A short-lived sensitization may have been overlooked under these temporal restrictions. Conditioning SP in 10(-5) M but not in 10(-6) M concentration significantly increased the IS response of polymodal C fibres, by 58% on average (n = 14). SP did not excite the units. Comparing with previous data, we conclude that there is a significant synergism between inflammatory mediators, acting to induce more intense and more sustained discharge via many nociceptors than single mediators alone could achieve. Conditioning substance P can further enhance this algogenic action. Mechanisms of interaction and relative contributions of single substances remain to be elucidated.
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PMID:Excitation of cutaneous afferent nerve endings in vitro by a combination of inflammatory mediators and conditioning effect of substance P. 128 91

Pieces of hairy skin tissue of fetal rat were transplanted into the anterior eye chamber of adult rats. The ability of autonomic and sensory nerve fibers from the host iris to innervate the grafted skin tissue was immunohistochemically and enzyme-histochemically examined using antisera against tyrosine hydroxylase (TH), substance P (SP), calcitonin gene-related peptide (CGRP) and vasoactive intestinal peptide (VIP), and a reaction medium for acetylcholinesterase (AchE). The grafted tissue was successfully implanted and connected with the host iris. Epidermis, dermis, subcutaneous tissue, hairs, hair follicles, sebaceous glands, and piloerector muscles developed in the graft. Two weeks after transplantation, TH-, SP-, and CGRP-immunoreactive fibers were observed in association with the blood vessels in the graft. Four weeks after transplantation, TH-immunoreactive fibers were distributed in the piloerector muscles, whereas SP- and CGRP-immunoreactive fibers were present around the hair follicles. VIP-immunoreactive and AchE-positive fibers were restricted to the host iris at all survival times. These results suggest that the outgrowth of autonomic and sensory nerve fibers from the host iris show target specificity for the grafted skin tissue.
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PMID:Target-specific innervation by autonomic and sensory nerve fibers in hairy fetal skin transplanted into the anterior eye chamber of adult rat. 172 32

Histochemical, immunocytochemical, and radioenzymatic techniques were used to examine the neurotransmitter-related properties of the innervation of thoracic hairy skin in rats during adulthood and postnatal development. In the adult, catecholamine-containing fibers were associated with blood vessels and piloerector muscles, and ran in nerve bundles throughout the dermis. The distribution of tyrosine hydroxylase (TH)-immunoreactive (IR) fibers was identical. Neuronal fibers displaying neuropeptide Y (NPY) immunoreactivity were seen in association with blood vessels. Double-labeling studies suggested that most, if not all, NPY-IR fibers were also TH-IR and likewise most, if not all, vessel-associated TH-IR fibers were also NPY-IR. Calcitonin gene-related peptide (CGRP)-IR fibers were observed near and penetrating into the epidermis, in close association with hair follicles and blood vessels, and in nerve bundles. A similar distribution of substance P (SP)-IR fibers was evident. In adult animals treated as neonates with the sympathetic neurotoxin 6-hydroxydopamine, a virtual absence of TH-IR and NPY-IR fibers was observed, whereas the distribution of CGRP-IR and SP-IR fibers appeared unaltered. During postnatal development, a generalized increase in the number, fluorescence intensity, and varicose morphology of neuronal fibers displaying catecholamine fluorescence, NPY-IR, CGRP-IR, and SP-IR was observed. By postnatal day 21, the distribution of the above fibers had reached essentially adult levels, although the density of epidermal-associated CGRP-IR and SP-IR fibers was significantly greater than in the adult. The following were not evident in thoracic hairy skin at any timepoint examined: choline acetyltransferase activity, acetylcholinesterase histochemical staining or immunoreactivity, fibers displaying immunoreactivity to vasoactive intestinal peptide, cholecystokinin, or leucine-enkephalin. The present study demonstrates that the thoracic hairy skin in developing and adult rats receives an abundant sympathetic catecholaminergic and sensory innervation, but not a cholinergic innervation.
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PMID:Postnatal development of autonomic and sensory innervation of thoracic hairy skin in the rat. A histochemical, immunocytochemical, and radioenzymatic study. 197 33

Non-hairy and hairy human skin were investigated with the use of the indirect immunohistochemical technique employing antisera to different neuronal and non-neuronal structural proteins and neurotransmitter candidates. Fibers immunoreactive to antisera against neurofilaments, neuron-specific enolase, myelin basic protein, protein S-100, substance P, neurokinin A, neuropeptide Y, tyrosine hydroxylase and vasoactive intestinal polypeptide hydroxylase and vasoactive intestinal polypeptide (VIP) were detected in the skin with specific distributional patterns. Neurofilament-, neuron-specific enolase-, myelin basic protein-, protein S-100, neuropeptide Y-, tyrosine hydroxylase- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities were found in or in association with sensory nerves; moreover, neuron-specific enolase-, myelin basic protein-, protein S-100, neuropeptide Y-, tyrosine hydroxylase- and vasoactive intestinal polypeptide (VIP)-like immunoreactivities occurred in or in association with autonomic nerves. It was concluded that antiserum against neurofilaments labels sensory nerve fibers exclusively, whereas neuron-specific enolase-, myelin basic protein- and protein S-100-like immunoreactivities are found in or in association with both sensory and autonomic nerves. Substance P- and neurokinin A-like immunoreactivities were observed only in sensory nerve fibers, and neuropeptide Y- and tyrosine hydroxylase-like immunoreactivities occurred only in autonomic nerve fibers, whereas vasoactive intestinal polypeptide (VIP)-like immunoreactivities was seen predominantly in autonomic nerves, but also in some sensory nerve fibers.
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PMID:Sensory and autonomic innervation of non-hairy and hairy human skin. An immunohistochemical study. 241 23

Immunocytochemistry against neuropeptides contained within primary afferent neurons was used to study the morphology and distribution of intraepidermal free nerve endings in cat facial skin. Calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity was found in similar intraepidermal nerve endings of cat glabrous and hairy skin epithelia. The greatest density of immunoreactive intraepidermal nerve endings was located in the nose epidermis. Small limited areas with immunoreactive intraepidermal nerve endings were also found in facial hairy skin.
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PMID:Presence of calcitonin gene-related peptide (CGRP) and substance P (SP) immunoreactivity in intraepidermal free nerve endings of cat skin. 245 51

Factors involved in the outcome of regeneration of the saphenous nerve after a cut or crush lesion were studied in adult rats with electrophysiological recordings of low-threshold mechanoreceptor activity and plasma extravasation of Evans blue after electrical nerve stimulation that activated C fibers. In the first series of experiments, saphenous and sciatic nerve section was combined with anastomosis of the transected proximal end of the saphenous nerve to the distal end of the cut tibial nerve. Regeneration of saphenous nerve fibers involved in plasma extravasation and low-threshold mechanoreceptor activity in the glabrous skin was observed 13 weeks after nerve anastomosis. Substance P-, calcitonin gene-related peptide-, and protein gene product 9.5 (PGP-9.5)-immunoreactive (IR) thin epidermal and dermal nerve endings, as well as coarse dermal PGP-9.5-IR nerve fibers and Meissner corpuscles and Merkel cell-neurite-like complexes, were observed in the reinnervated glabrous skin at this time. In a second series of experiments, the time course of the regeneration of saphenous nerve axons to the permanently sciatic-nerve-denervated foot sole was examined. Saphenous-nerve-induced plasma extravasation and low-threshold mechanoreceptor activity in the saphenous nerve were found in the normal saphenous nerve territory 2, 3, 4, and 6 weeks after sciatic nerve cut combined with saphenous nerve crush in the left hindlimb. Saphenous-nerve-induced plasma extravasation was also present in the glabrous skin normally innervated by the sciatic nerve 3, 4, and 6 weeks after the sciatic cut/saphenous crush lesion. However, no low-threshold mechanoreceptor activity was detected in the saphenous nerve when the glabrous skin area was stimulated. In a third series of experiments, the fate of the expansion of the saphenous nerve territory after saphenous nerve crush was examined when the crushed sciatic nerve had been allowed to regenerate. Nerve fibers involved in plasma extravasation were observed in the glabrous skin of the hindpaw after saphenous nerve, as well as after tibial nerve, C-fiber stimulation 3, 12, and 43 weeks after the saphenous crush/sciatic crush lesion. Low-threshold mechanoreceptors from the regenerated saphenous nerve, which primarily innervates hairy skin, seem to be functional in the glabrous skin if the axons are guided by the transected tibial nerve by anastomosis. Furthermore, the results indicate that fibers from the regenerating saphenous nerve that have extended into denervated glabrous skin areas can exist even if sciatic nerve axons are allowed to grow back to their original territory.
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PMID:Time course and characteristics of the capacity of sensory nerves to reinnervate skin territories outside their normal innervation zones. 831 Jul 81

1. The relationship between the afferent properties and substance P-like immunoreactivity (SP-LI) of L6 and S1 dorsal root ganglion (DRG) neuronal somata was examined in anaesthetized guinea-pigs. Glass pipette microelectrodes filled with fluorescent dyes were used to make intracellular recordings and to label DRG somata. The dorsal root conduction velocity (CV) and the afferent receptive properties of each unit were categorized according to criteria established in other species. Categories included a variety of low threshold mechanoreceptive classes, innocuous thermoreceptive and several nociceptive classes. Nociceptive units were further subdivided on the basis of CV and the locus of the receptive field (superficial cutaneous, deep cutaneous or subcutaneous). 2. SP-LI was determined using the avidin-biotin complex method and the relative staining intensity determined by image analysis. The possible significance of labelling intensity is discussed. Clear SP-LI appeared in twenty-nine of 117 dye-labelled neurones. All SP-LI positive units with identified receptive properties were nociceptive but not all categories of nociceptors were positive. The intensity of SP-LI labelling varied, often systematically, in relation to afferent properties. There was a tendency for nociceptive neurones with slower CVs and/or smaller cell bodies to show SP-LI. 3. Nineteen of fifty-one C fibre neurones showed SP-LI. Fewer than half the C polymodal nociceptors (CPMs) were positive. The most intensely labelled units were the deep cutaneous nociceptors and some of the CPMs in glabrous skin. C low threshold mechanoreceptors and cooling-sensitive units did not show SP-LI. 4. Ten of sixty-six A fibre neurones exhibited SP-LI, including eight of sixteen A delta nociceptors and two of fifteen A alpha/beta nociceptors. A fibre neurones exhibiting SP-LI included seven of eight deep cutaneous mechanical nociceptors and some superficial cutaneous mechano-heat nociceptors of hairy skin. In contrast, none of twenty superficial cutaneous A high threshold mechanoreceptor units or the thirty-five A fibre low threshold units (D-hair and other units) showed detectable SP-LI. 5. We conclude that SP-LI labelling in guinea-pig DRG neurones is related to (a) afferent receptive properties, (b) the tissue in which the peripheral receptive terminals are located, (c) the CV and (d) the soma size.
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PMID:Relationship of substance P to afferent characteristics of dorsal root ganglion neurones in guinea-pig. 940 65

By intravenous application of the specific neurokininl receptor antagonist SR 140333 and the specific calcitonin gene-related peptide receptor antagonist CGRP8-37 we tested to what extent neurokinins (substance P, neurokinin A) and calcitonin gene-related peptide are involved in mediating antidromic vasodilatation in skin of anaesthetized Wistar rats. The lumbar sympathetic chain was sectioned bilaterally between ganglia L2 and L3 to remove ongoing vasoconstrictor activity to the hindquarter. The left dorsal root L5 was stimulated electrically at 1 Hz with 20 pulses supramaximal for activating C-fibres to evoke antidromic vasodilatation which was measured with laser Doppler flowmetry on the glabrous plantar skin and the hairy skin of the lower hindlimb within the left L5 territory. Stimulation-induced vasodilatation was tested after applying SR 140333 (0.1 mg/kg) and CGRP8-37 (0.3 mg/kg) alone or in combination. SR 140333 delayed the onset of the vasodilatation, but did not change its amplitude. CGRP8-37 reduced the amplitude and duration of the vasodilatation, but did not affect the latency of its onset. In combination, SR 140333 potentiated the effect of CGRP8-37 on the amplitude of the vasodilatation in glabrous but not in hairy skin and CGRP8-37 potentiated the delayed onset produced by SR 140333 in both cutaneous tissues. Antidromic vasodilatation in glabrous skin was almost totally blocked by SR 140333 (0.1 mg/kg) in combination with CGRP8-37 (0.45 mg/kg), but a substantial dilatation remained in hairy skin. It is concluded that in rat glabrous skin the vasodilatation evoked by a low level of activity in small-diameter primary afferents is likely to result from the release and synergistic action of neurokinins (substance P and/or neurokinin A) and calcitonin gene-related peptide, while in hairy skin neurokinins are involved to a minor extent only.
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PMID:Involvement of neurokinins in antidromic vasodilatation in hairy and hairless skin of the rat hindlimb. 1036 13

The innervation of the digits on the raccoon forepaw was examined by using immunochemistry for protein gene product 9.5, calcitonin-gene related peptide, substance P, neuropeptide-Y, tyrosine hydroxylase, and neurofilament protein. The larger-caliber axons in the ventral glabrous skin terminate as Pacinian corpuscles deep in the dermis, small corpuscles and Merkel endings around the base of dermal papillae, and Merkel endings on rete pegs in dermal papillae. Extensive fine-caliber innervation terminates in the epidermis and on the microvasculature. The innervation is more dense in the distal than in the proximal volar pads. Pacinian endings are also concentrated in the transverse crease separating the distal and proximal pads. In the dorsal hairy skin, hair follicles are well innervated with piloneural complexes. Merkel innervation is located under slight epidermal elevations and in some large Merkel rete pegs located at the apex of transverse skin folds just proximal to the claw. No cutaneous Ruffini corpuscles were found anywhere on the digit. The claw is affiliated with dense medial and lateral beds of Pacinian endings, bouquets of highly branched Ruffini-like endings at the transition from the distal phalanx and unmyelinated innervation in the skin around the perimeter. Encapsulated endings are located at the lateral edge of the articular surface of the distal phalanx. Extensive fine-caliber innervation is affiliated with sweat glands and with the vasculature and is especially dense at presumptive arteriovenous sphincters. Virtually all of the sweat gland and vascular innervation is peptidergic, whereas most of the unmyelinated epidermal innervation is nonpeptidergic.
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PMID:Innervation of the digit on the forepaw of the raccoon. 1070 67

The present study examines the occurrence of calcitonin gene-related peptide-, substance P- and tyrosine hydroxylase-like immunoreactive profiles in glabrous and hairy foot skin from normal and nerve-injured rats. After neurotomy/suture, glabrous skin samples contain few calcitonin gene-related peptide-, substance P- and tyrosine hydroxylase-like immunoreactive profies. The number of calcitonin gene-related peptide- and substance P-like immunoreacive profiles in the epidermis is significantly subnormal. Hairy skin from these rats does also contain few calcitonin gene-related peptide-, substance P- and tyrosine hydroxylase-like immunoreactive profiles. In addition, the presence of epidermal calcitonin gene-related peptide-like imunoreactive profiles in glabrous skin is subnormal on the contralateral side. After nerve crush injury, the occurrence of calcitonin gene-related peptide-like, but not substance P-like, immunoreactive profiles in th epidermis of the glabrous skin is significantly subnormal. The occurrence of tyrosine hylase-like immnunoreactive fibres in relation to the digital artery is also subnormal. The occurrence in hairy skin of calcitonin gene-related peptide-like immunoreactive, substance P-like immunoreactive and tyrosine hydroxylase-like immunoreactive profiles is subnormal. In both skin types, the contralateral occurrence of such profiles is subjectively normal. These results show that the occurrence of calcitonin gene-related peptide-, substance P-, and tyrosine hydroxylase-like immunoreactive profiles in glabrous and hairy foot skin is clearly subnormal after neurotomy and suture and less abnormal after nerve crush. After neurotomy and suture the contralateral side is also affected.
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PMID:Regeneration of putative sensory and sympathetic cutaneous nerve endings in the rat foot after sciatic nerve injury. 1097 Jan 10


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