Pharmacological receptors for substance P and neurokinins

Regoli, Doménico; Drapeau, Guy; Dion, S.; D’Orléans-Juste, Pedro

doi:10.1016/0024-3205(87)90349-3

Cited by 322 publications

(92 citation statements)

References 13 publications

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“…The tachykinin (TK) receptors (NK1, NK2, NK3) have been defined on the basis of their sensitivity to the natural peptides, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) and to a number of synthetic TK agonists selective for one of the three TK receptors (Buck et al, 1984; Lee et al, 1986;Drapeau et al, 1987;Dion et al, 1987;Regoli et al, 1987;Maggi et al, 1987;Rovero et al, 1989). The identification, through cloning studies of three receptor proteins belonging to the G-protein superfamily, which possess the pharmacological character of the above receptors, supports this classification (Masu et al, 1987;Yokota et al, 1989;Hershey & Krause, 1990).…”

Section: Introductionmentioning

confidence: 99%

Further evidence for the existence of NK₂ tachykinin receptor subtypes

Patacchini¹,

Astolfi

Quartara

et al. 1991

British J Pharmacology

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We have evaluated the biological activity of a number of neurokinin A (4–10), (NKA (4–10)) analogues in the endothelium‐deprived rabbit isolated pulmonary artery (RPA) and hamster isolated trachea (HT), two tissues rich in different NK2 receptor subtypes. MDL 28,564, a pseudopeptide selective for NK2 receptor sites, behaved as a full agonist in the RPA, while in the HT it competitively antagonized NKA or [βAla8]‐NKA (4–10) contractile effects. The peculiar behaviour of MDL 28,564 in the RPA and HT may be explained neither by a difference in receptor reserve between the two organs (the reserve being three times greater in RPA than in the HT) nor by a different affinity for the two receptor subtypes (identical dissociation constants, pKA or pKB, calculated in the RPA and in the HT). On the other hand, MDL 28,564 displayed a very different intrinsic efficacy for the two receptor subtypes. The novel peptides MEN 10,295 ([Trp7, βAla8]‐NKA‐(4–10)) and MEN 10,296 ([Tyr5, Trp7, βAla8]‐NKA‐(4–10)) behaved as weaker agonists than MDL 28,564 in the RPA, but retained appreciable agonist activity also in the HT. The novel peptides: MEN 10,282 ([Tyr5, d‐Trp6,8, Trp9, Arg10]‐NKA‐(4–10)), MEN 10,449 ([diI‐Try5, d‐Trp6,8,9, Arg10]‐NKA‐(4–10)) and the cyclic hexapeptide L 659,877 (cyclo [Leu‐Met‐Gln‐Trp‐Phe‐Gly]) behaved as competitive antagonists against NKA contractile effects both in the RPA and HT. MEN 10,282 and MEN 10,449 were unable to distinguish between the NK2 receptor subtypes, having almost the same affinity in the two organs. On the other hand L 659,877 was about 15 times more potent in the HT than in the RPA. These results provide further evidence for NK2 receptors heterogeneity and are useful in outlining pharmacological features of the two subtypes present in the RPA and HT.

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Section: Introductionmentioning

confidence: 99%

Further evidence for the existence of NK₂ tachykinin receptor subtypes

Patacchini¹,

Astolfi

Quartara

et al. 1991

British J Pharmacology

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“…The evidence for this proposal has come, until comparatively recently, almost exclusively from the determination of activities of naturally-occurring tachykinin agonists including the mammalian neurokinins, substance P (SP), neurokinin A (NKA) and neurokinin B (NKB) in functional studies in the periphery and radio-ligand binding studies both in the periphery and in the CNS (for reviews see, Watson, 1984;Lee et al, 1986;Regoli et al, 1987;Quirion & Dam, 1988).…”

Section: Introductionmentioning

confidence: 99%

Novel selective agonists and antagonists confirm neurokinin NK₁ receptors in guinea‐pig vas deferens

Hall

Morton

1991

British J Pharmacology

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1 This study investigated the recognition characteristics of neurokinin receptors mediating potentiation of the contractile response to field stimulation in the guinea-pig vas deferens.2 A predominant NK, receptor population is strongly suggested by the relative activities of the common naturally-occurring tachykinin agonists, which fall within less than one order of magnitude. This conclusion is supported by the relative activities of the synthetic NK, selective agonists substance P methyl ester, [Glp6,L-Pro9]-SP(6, 1) and 6-aminovaleryl-[L-Pro9,N-MeLeul']-SP(7 ,l) (GR73632) which were 0.78, 9.3 and 120 as active as substance P, respectively. Furthermore, the NK2 selective agonist [Lys3, Gly8,-R-y-lactam-Leu9]-NKA(3,0) (GR64349) was active only at the highest concentrations tested Trpl 1]-SP(1-1) (GR71251) did not produce agonist-dependent pKB estimates. Schild plot analysis indicated a competitive interaction with a single receptor population where the antagonist had an estimated overall pKB of 7.58 + 0.13 for the four agonists of differing subtype selectivity tested (GR73632, GR64349, substance P methyl ester and neurokinin B). This estimate is similar to that we obtained for NK1-mediated (substance P methyl ester) contraction in the guinea-pig ileum preparation (pKB= 7.86 + 0.05).5 Tachykinin action appears not to depend on release of a number of intermediary mediators including acetylcholine, histamine or cyclo-oxygenase products, nor to involve interaction with neuronal mechanisms including a2-adrenoceptor feedback, noradrenergic Uptake-I or opioid-release, since antagonism or inhibition of these mechanisms did not modify responses to tachykinins. 6 We conclude that tachykinin action in the field-stimulated guinea-pig vas deferens preparation is mediated through interaction with a predominant neurokinin NK, receptor population and this preparation can therefore be used to study NK, modulation of sympathetic neurotransmission.

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“…For the NK1 receptor the sequence of affinities of the preferred neurokinins is SP = HK-1 > NPG > NKA = NPK > NKB [184] [197]. For the NK2 receptor the binding of tachikinins has been described in the following rank order: NPK = NPG > NKA > NKB > SP [17] [192].…”

Section: Mammalian Neurokinins and Their Receptorsmentioning

confidence: 99%

Neuropeptide Receptors in Pain Circuitries: Useful Targets for CNS Imaging with Non-Peptide Ligands Suitable for PET?

Pissarek¹

2014

WJNS

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Pharmacological receptors for substance P and neurokinins

Cited by 322 publications

References 13 publications

Further evidence for the existence of NK₂ tachykinin receptor subtypes

Further evidence for the existence of NK₂ tachykinin receptor subtypes

Novel selective agonists and antagonists confirm neurokinin NK₁ receptors in guinea‐pig vas deferens

Neuropeptide Receptors in Pain Circuitries: Useful Targets for CNS Imaging with Non-Peptide Ligands Suitable for PET?

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Pharmacological receptors for substance P and neurokinins

Cited by 322 publications

References 13 publications

Further evidence for the existence of NK2 tachykinin receptor subtypes

Further evidence for the existence of NK2 tachykinin receptor subtypes

Novel selective agonists and antagonists confirm neurokinin NK1 receptors in guinea‐pig vas deferens

Neuropeptide Receptors in Pain Circuitries: Useful Targets for CNS Imaging with Non-Peptide Ligands Suitable for PET?

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Further evidence for the existence of NK₂ tachykinin receptor subtypes

Further evidence for the existence of NK₂ tachykinin receptor subtypes

Novel selective agonists and antagonists confirm neurokinin NK₁ receptors in guinea‐pig vas deferens