Autoradiographic localization of substance P binding sites in rat footpad skin

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

doi:10.1016/0304-3940(89)90199-7

Cited by 28 publications

(5 citation statements)

References 14 publications

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“…However, the presence of specific peptide receptors in the mast cell membrane is questionable. Peptide concentrations in the micromolar range are necessary to induce mast cell degranulation and both studies of structure–activity relationships and receptor autoradiography failed to detect specific peptide receptors on mast cells ( Repke and Bienert, 1987 ; Repke et al, 1987 ; O'Flynn et al, 1989 ; Mousli et al, 1994 ). In view of these difficulties, Mousli et al (1990 b ) proposed a direct interaction of cationic peptides with heterotrimeric G proteins without the participation of a receptor.…”

Section: Introductionmentioning

confidence: 99%

Mechanism of Peptide-induced Mast Cell Degranulation

Lorenz¹,

Wiesner²,

Zipper³

et al. 1998

The Journal of General Physiology

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Substance P and other polycationic peptides are thought to stimulate mast cell degranulation via direct activation of G proteins. We investigated the ability of extracellularly applied substance P to translocate into mast cells and the ability of intracellularly applied substance P to stimulate degranulation. In addition, we studied by reverse transcription–-PCR whether substance P-specific receptors are present in the mast cell membrane. To study translocation, a biologically active and enzymatically stable fluorescent analogue of substance P was synthesized. A rapid, substance P receptor- and energy-independent uptake of this peptide into pertussis toxin-treated and -untreated mast cells was demonstrated using confocal laser scanning microscopy. The peptide was shown to localize preferentially on or inside the mast cell granules using electron microscopic autoradiography with 125I-labeled all-D substance P and 3H-labeled substance P. Cell membrane capacitance measurements using the patch-clamp technique demonstrated that intracellularly applied substance P induced calcium transients and activated mast cell exocytosis with a time delay that depended on peptide concentration (delay of 100–500 s at concentrations of substance P from 50 to 5 μM). Degranulation in response to intracellularly applied substance P was inhibited by GDPβS and pertussis toxin, suggesting that substance P acts via G protein activation. These results support the recently proposed model of a receptor-independent mechanism of peptide-induced mast cell degranulation, which assumes a direct interaction of peptides with G protein α subunits subsequent to their translocation across the plasma membrane.

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Section: Introductionmentioning

confidence: 99%

Mechanism of Peptide-induced Mast Cell Degranulation

Lorenz¹,

Wiesner²,

Zipper³

et al. 1998

The Journal of General Physiology

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“…The identity of further tachykinin receptors, however, awaits confirmation by molecular cloning. Substance P effects on dermal vascular function are predominantly mediated by the NKl receptor type [28] and receptor-like binding sites for substance P have been localised by in vitro receptor autoradiography to vascular structures in both human and rat skin [29,30]. The recent development of potent and selective NKl receptor antagonists has confirmed the role of substance P in dermal vascular regulation [15], but has also revealed marked interspecics variations in receptor selectivity [31].…”

Section: Neurovascular Regulatory Factors Of the Skin The Tachykininsmentioning

confidence: 94%

“…CGRP 1 receptors are inhibited by long carboxy-terminal fragments of CGRP such as CGRP (18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37), while CGRP 2 receptors are activated by the agonist [Cys(ACM)2-^]huCGRP [40]. CGRP-enhanced plasma extravasation in the skin is inhibited by CGRP{ 18-37) and appears, therefore, to be mediated by the CGRPl subtype [41].…”

Section: Neurovascular Regulatory Factors Of the Skin The Tachykininsmentioning

confidence: 99%

Neural and vascular regulatory factors of the skin

Walsh

Terenghi

Polak

1994

Acad Dermatol Venereol

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Bacl^round Neural and vascular factors regulate many aspects of dermal funetion, including blood flow, inflammation, tissue repair and eccrine secretion. Abnormalities of neurovascular regulation may contribute to dermatological manifestations of a wide range of diseases including psoriasis, nodular prurigo and leprosy, diabetes mellitus and Raynaud's disease. Aims In this review we diseuss evidence for roles played by neural and vascular regulatory faetors in skin, with particular reference to the regulatory peptides substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, neuropeptide Y and endothelin and to the important endothelial cell product nitric oxide. Conclusions An understanding of the anatomical basis of neurovascular regulation and the changes which occur during disease may lead to novel diagnostic and prognostic tests for dermatological eonditions, while an understanding of speeific reeeptors mediating the actions of regulatory peptides will lead to the development of specific antagonists as a novel approach in clinical dermatology.

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“…SP is very potent in increasing vascular permeability in the skin. Postcapillary venules (G. Jancs6 1984;Kenms et al 1984;Kowalski et al 1990;Gao et al 1991) wl~ch bear NK 1 receptors (Deguchi et O'Flynn et al 1989) are the common target of action of antidromic nerve stimulation and SP in increasing vascular permeability. The exudative responses to antidromic nerve stimulation and SP are similar with regard to pharmacology (Chahl 1979;Lembeck and Holzer 1979;Morton and Chahl 1980;Khalil and Helme 1989b) and time course inasmuch as the early phase of extravasation is due to a direct action on venular endothelial cells whilst later phases involve secondary mediators such as histamine, 5-hydroxytryptamine and prostanoids (Chahl 1979;Morton and Chahl 1980;Kowalski and Kaliner 1988;Khalil and Helme 1989b;Kowalski et al 1990).…”

Section: Role Of Sp In Afferent Nerve-mediated Protein Extravasationmentioning

confidence: 99%

“…The different nature of the mast cell receptor for SP is underlined by the absence of autoradiographically demonstrable NK I receptor sites from mast ceils in the rat footpad skin (O'Flynn et al 1989). Biochemical evidence suggests that SP's action on mast cells is not mediated by a proper membrane receptor for the peptide but results from a direct interaction of SP with G proteins in the mast cell membrane (Bueb et al 1990).…”

Section: Nature Of the Mast Cell Receptors For Spmentioning

confidence: 99%