Substance P antagonists active in vitro and in vivo

Mizrahi, Jacques; Escher, Emanuel; Caranikas, Stephanos; D’Orléans-Juste, Pedro; Regoli, Doménico

doi:10.1016/0014-2999(82)90561-1

Cited by 55 publications

(20 citation statements)

References 7 publications

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“…However, the substance P an tagonist [Z)-Pro4,i>-Trp7-9-,0]SP4_n does act as an antagonist to substance P in human skin [17,18]. This antagonist inhibits the flare induced by substance P but does not inhibit the wheal, confirming the studies with agonists which show that substance P produces wheal and flare by an action at dif ferent sites.…”

Section: Action Of Neuropeptides In Human Skinsupporting

confidence: 73%

The Skin as an Organ for the Study of the Pharmacology of Neuropeptides

Jc¹

1988

Skin Pharmacol Physiol

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There is good evidence that some vascular effects of inflammation in the skin are neurogenic and involve axon reflexes in the terminal arborizations of C-fibres containing substance P, neurokinin A and calcitonin gene-related peptide (CGRP). Substance P produces dose-related wheal and flare reactions in human skin. Neurokinin A induces wheal but little or no flare and is less potent than substance P. CGRP induces both wheal and flare but is also less potent than substance P. In addition, CGRP induces a slow-onset, intense vasodilatation in human skin which persists for several hours and is associated with leucocyte infiltration: a response which is not seen with substance P. Substance P also releases histamine from mast cells in the skin and the presence or absence of a role for histamine and mast cells in neurogenic inflammation in skin is discussed.

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Section: Action Of Neuropeptides In Human Skinsupporting

confidence: 73%

The Skin as an Organ for the Study of the Pharmacology of Neuropeptides

Jc¹

1988

Skin Pharmacol Physiol

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“…In this paper we describe the effects of an antagonist of substance P in rat mast cells and human skin which has been previously shown to be an antagonist in some smooth muscle preparations [7,9]. Also we examine the activity of some selective agonists at substance P receptors in an attempt to evaluate the mast cell receptor in the context of the proposed 'P' and 'E' subtypes.…”

Section: Introductionmentioning

confidence: 98%

“…Receptor classification on the basis of agonist activities is known to be unreliable and hence classification by means of antagonist affinities is desirable. There are presently a number of structural analogues of substance P for which antagonist activity have been reported [5][6][7][8][9]. Using these, some attempts at receptor classification have been made, though the results of these studies do no yet present a clear picture.…”

Section: Introductionmentioning

confidence: 99%

The substance P receptor on rat mast cells and in human skin

et al. 1984

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(D-Pro4 D- Trp7 ,9,10)SP4-11 (SPA) has been shown to be a competitive antagonist of the histamine releasing action of substance P in rat peritoneal mast cells. Antagonist activity of SPA is expressed in the concentration range 1 to 10 microM, but at higher concentrations SPA releases histamine. SPA inhibits the flare response induced by substance P in human skin but is without effect on the wheal response. Up to 12.5 pmol SPA produces neither wheal nor flare response by itself. The structurally related peptide, kassinin , does not cause histamine release from rat mast cells at concentrations up to 10 microM whereas the methyl ester of substance P was found to 1.6 times more active than substance P in this respect. The findings are discussed in terms of the classification of substance P receptors and the mechanism of wheal and flare in human skin.

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“…The present work aims to study further the receptor mediating acetylcholine release by examining the effects of three substance P antagonists on the actions of eledoisin alone. The three analogues used were [D-Pro4,D-Trp7'9"']SPP4 I) (Mizrahi et al, 1982), [D-Arg ,D-Pro2,D-Trp '9,Leul ']SP(, l (Rosell et al, 1983a) and [D-Arg',D-Trp79,Leu']SP(j 1), which has been termed spantide (Rosell et al, 1983b). We have extensively studied the first two (Bailey et al, 1983;1985) with respect to their activities against the tachykinins in a variety of smooth muscle preparations.…”

Section: Introductionmentioning

confidence: 99%

A comparison of the effects of three substance P antagonists on tachykinin‐stimulated [³H]‐acetylcholine release in the guinea‐pig ileum

Featherstone

Fosbraey

Morton

1986

British J Pharmacology

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Trp7'9,Leul ']SP( 1) and [D-Arg',D-Trp7 9'Leu' 'JSP(j Ij) (spantide) against eledoisin were examined in the guinea-pig ileum myenteric plexus, where a continuous superfusion system was employed to examine evoked release of [3H]-acetylcholine ([3H]-ACh]); effects on mechanical activity of the preparations were also measured. 2 Eledoisin was chosen as the standard tachykinin agonist since the rank order ofpotency observed in evoking release was eledoisin, kassinin, substance P, physalaemin; on this basis is may be presumed that an 'SP-E' type receptor was involved in the release process. 3 The two undecapeptide antagonists both significantly reduced the response to eledoisin (10 nM) as assessed by both [3H]-ACh release and mechanical activity which under these conditions was largely dependent on ACh release, and the response levels could be restored by increasing the concentration of eledoisin to 100 nM. The pA2 values for the two antagonists were estimated as 5. ,) being the most active in this respect, a 10 gM concentration producing 50% of the response seen with 10 nM eledoisin. 5 These findings are discussed both in relation to tachykinin receptor classifications and limitations in the use of such antagonists in the study of the role of tachykinins in neurotransmission.

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Substance P antagonists active in vitro and in vivo

Cited by 55 publications

References 7 publications

The Skin as an Organ for the Study of the Pharmacology of Neuropeptides

The Skin as an Organ for the Study of the Pharmacology of Neuropeptides

The substance P receptor on rat mast cells and in human skin

A comparison of the effects of three substance P antagonists on tachykinin‐stimulated [³H]‐acetylcholine release in the guinea‐pig ileum

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Substance P antagonists active in vitro and in vivo

Cited by 55 publications

References 7 publications

The Skin as an Organ for the Study of the Pharmacology of Neuropeptides

The Skin as an Organ for the Study of the Pharmacology of Neuropeptides

The substance P receptor on rat mast cells and in human skin

A comparison of the effects of three substance P antagonists on tachykinin‐stimulated [3H]‐acetylcholine release in the guinea‐pig ileum

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Product

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A comparison of the effects of three substance P antagonists on tachykinin‐stimulated [³H]‐acetylcholine release in the guinea‐pig ileum