Autoradiographic localization of substance P binding sites in rat footpad skin

O'Flynn, N.M.; Watkins, Dianne J.; Helme, Robert D.; Burcher, Elizabeth

doi:10.1016/0167-0115(88)90356-4

Cited by 10 publications

(11 citation statements)

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“…With careful visual observation of the material, we suggest that, although NK-1 receptors are present on arterioles, the intensity of labeling is less than on venules, suggesting the presence of fewer NK-1 receptors on arterioles, whereas CGRP receptors may be more abundant on arterioles. Our results are in accordance with those of other researchers who have identified NK-1r binding sites on blood vessel endothelial and smooth muscle cells (O'Flynn et al, 1989), with less intense smooth muscle cell labeling compared with endothelial cell labeling. We also detected NK-1r on pericytic cells.…”

Section: Nk-1 Receptors Are Expressed On Blood Vessel Wallssupporting

confidence: 96%

“…Because most of the effects of SP are mediated through NK-1r, it was believed that these receptors were expressed on the cell membrane of mast cells. We did not detect the presence of NK-1r on mast cells, in accordance with the results obtained by O'Flynn et al (1989). This reinforces the observation that SP-induced mast cell activation is receptor-independent and occurs by direct interaction of SP's N-terminal basic residues with G-proteins on mast cell plasma membranes (Bueb et al, 1990).…”

Section: Nk-1 Receptors Are Expressed On Blood Vessel Wallssupporting

confidence: 94%

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Light and electron microscopic study of the distribution of substance P‐immunoreactive fibers and neurokinin‐1 receptors in the skin of the rat lower lip

Ruocco

Cuello

Shigemoto

et al. 2001

J of Comparative Neurology

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Cutaneous antidromic vasodilatation and plasma extravasation, two phenomena that occur in neurogenic inflammation, are partially blocked by substance P (SP) receptor antagonists and are known to be mediated in part by mast cell-released substances, such as histamine, serotonin, and nitric oxide. In an attempt to provide a morphological substrate for the above phenomena, we applied light and electron microscopic immunocytochemistry to investigate the pattern of SP innervation of blood vessels and its relationship to mast cells in the skin of the rat lower lip. Furthermore, we examined the distribution of SP (neurokinin-1) receptors and their relationship to SP-immunoreactive (IR) fibers. Our results confirmed that SP-IR fibers are found in cutaneous nerves and that terminal branches are observed around blood vessels and penetrating the epidermis. SP-IR fibers also innervated hair follicles and sebaceous glands. At the ultrastructural level, SP-IR varicosities were observed adjacent to arterioles, capillaries, venules, and mast cells. The varicosities possessed both dense core vesicles and agranular synaptic vesicles. We quantified the distance between SP-IR varicosities and blood vessel endothelial cells. SP-IR terminals were located within 0.23-5.99 microm from the endothelial cell layer in 82.7% of arterioles, in 90.2% of capillaries, and in 86.9% of venules. Although there was a trend for SP-IR fibers to be located closer to the endothelium of venules, this difference was not significant. Neurokinin-1 receptor (NK-1r) immunoreactivity was most abundant in the upper dermis and was associated with the wall of blood vessels. NK-1r were located in equal amounts on the walls of arterioles, capillaries, and venules that were innervated by SP-IR fibers. The present results favor the concept of a participation of SP in cutaneous neurogenic vasodilatation and plasma extravasation both by an action on blood vessels after binding to the NK-1r and by causing the release of substances from mast cells after diffusion through the connective tissue.

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Section: Nk-1 Receptors Are Expressed On Blood Vessel Wallssupporting

confidence: 96%

Section: Nk-1 Receptors Are Expressed On Blood Vessel Wallssupporting

confidence: 94%

Light and electron microscopic study of the distribution of substance P‐immunoreactive fibers and neurokinin‐1 receptors in the skin of the rat lower lip

Ruocco

Cuello

Shigemoto

et al. 2001

J of Comparative Neurology

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“…SP in rat trachea [43]. There is evidence for the presence of NK1 binding sites on both endothelial cells and smooth muscle cells of arterioles [6,44]. These facts support our suggestion that the increase in dye leakage induced by i.v.…”

Section: Discussionsupporting

confidence: 59%

“…It is established that these neuropeptides interact with at least three classes of tachykinin receptor, termed NK1, NK2, and NK3 [4]. In particular, SP is known to cause skin inflammation by increasing vascular permeability through activation of NK 1 receptors on blood vessels [5,6] and by releasing vasoactive amines from mast cells [7,8]. Recent studies have shown that intradermal injection of SP into guinea-pig skin induces leukocyte accumulation which is dependent on the expression of the CD18 antigen on leukocytes [9].…”

Section: Introductionmentioning

confidence: 99%

Involvement of tachykinin receptors in oedema formation and plasma extravasation induced by substance P, neurokinin A, and neurokinin B in mouse ear

1996

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The involvement of tachykinin receptors in skin inflammation induced by substance P (SP), neurokinin A (NKA), and neurokinin B (NKB) was investigated in mouse ears. Intradermal injection of tachykinins (0.1-100 pmol/site) into the ear skin produced oedema formation. RP 67580 (ED50: 0.34 mg/kg, i.v.) and SR 140333 (ED50: 0.19 mg/kg, i.v.), the non-peptide NK1 receptor antagonists, inhibited SP-induced oedema. SR 140333 was also effective in preventing NKA- and NKB-induced oedema. SR 48968 (1 mg/kg, i.v.), a non-peptide NK2 antagonist, induced a significant inhibition of NKA-induced oedema but had no effect on the response to SP and NKB. SR 142801 (3 mg/kg, i.v.), a non-peptide NK3 antagonist, prevented only NKB-induced oedema. In contrast, phosphoramidon (0.1 and 0.5 mg/kg, i.v.), an endopeptidase inhibitor, enhanced the oedema response to tachykinins. SR 140333, SR 48968, and SR 142801 blocked the enhancement by phosphoramidon of the response to SP, NKA, and NKB, respectively. Plasma extravasation in ear skin was induced by i.v. injection of tachykinins (0.7-17.6 nmol/kg). RP 67580 (ED50: 0.15 mg/kg, i.v. for SP) and SR 140333 (ED50: 14.3 micrograms/kg, i.v. for SP) inhibited tachykinin-induced plasma extravasation in ear skin. However, SR 48968 and SR 140281 had no effect on the vascular response to tachykinins. Chlorpheniramine (4 mg/kg, i.v.), a histamine H1 blocker, inhibited the response to local SP but not to i.v. SP. These results suggest that in addition to the NK1 receptors, functional NK2 and NK3 receptors may participate in the oedema response to local NKA and NKB in the ear skin. However, it appears that NK1 receptors on blood vessels are involved predominantly in plasma extravasation induced by i.v. tachykinins in the ear.

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“…In contrast, pretreatment with SR 48968, a non-peptide NK2 receptor antagonist, at a dose sufficient to inhibit NK2 receptor agonist-induced protein leakage in guinea-pig lower airway [26], had no effect on capsaicin-induced oedema. Moreover, whilst it has been shown that NKA coexists with SP in rat primary sensory neurones [27] and is synthesized from the same precursor [28], an NKA binding site is not found in rat skin while SP binding sites exist in dermal papillae, postcapillary venules, sweat glands, and arterioles [29]. Furthermore, NK 1 receptor mRNA, but not NK2 receptor mRNA, is distributed and expressed in rat skin [30].…”

Section: Discussionmentioning

confidence: 97%

Involvement of substance P as a mediator in capsaicin-induced mouse ear oedema

1995

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We examined the involvement of substance P (SP) in mouse ear oedema induced by topical application of capsaicin (250 micrograms/ear). Reapplication of capsaicin at 4 h, 24 h, and 48 h after initial treatment did not induce a second oedema response. Oedema induced after the second application was significantly (p < 0.01 or p < 0.001) suppressed for up to 30 days but was observed when capsaicin was applied 40 days after initial treatment. Topical pretreatment of ears with capsaicin at 4 h, 24 h and 48 h before i.v. injection of SP (5 micrograms/kg) did not cause a significant inhibition of plasma extravasation in ear skin. NK1 receptor antagonists such as RP 67580 (ED50:0.19 mg/kg, i.v.), spantide II (ED50:0.33 mg/kg, i.v.), and GR 82334 (ED50:0.26 mg/kg, i.v.), inhibited capsaicin-induced ear oedema, whereas SR 48968 (2.0 mg/kg, i.v.), a NK2 receptor antagonist, had no effect. Furthermore, RP 67580 (0.5 kg/mg, i.v.) inhibited the oedema response induced by reapplication of capsaicin at 50 days after initial treatment. These results indicate that tachyphylaxis of capsaicin-induced oedema is reversible and suggest that this response may be due mainly to a reduction of SP in sensory neurones but not to any loss of responsiveness of NK1 receptors. We also conclude that SP and NK1 receptors are involved predominantly in the development of capsaicin-induced mouse ear oedema.

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Autoradiographic localization of substance P binding sites in rat footpad skin

Cited by 10 publications

References 0 publications

Light and electron microscopic study of the distribution of substance P‐immunoreactive fibers and neurokinin‐1 receptors in the skin of the rat lower lip

Light and electron microscopic study of the distribution of substance P‐immunoreactive fibers and neurokinin‐1 receptors in the skin of the rat lower lip

Involvement of tachykinin receptors in oedema formation and plasma extravasation induced by substance P, neurokinin A, and neurokinin B in mouse ear

Involvement of substance P as a mediator in capsaicin-induced mouse ear oedema

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