Pharmacological specificity of novel, synthetic, cyclic peptides as antagonists at tachykinin receptors

McKnight, A.T.; Maguire, Janet J.; Elliott, N.J.; Fletcher, Alan E.; Foster, Alan C.; Tridgett, R.; Williams, Brian J.; Longmore, J.; Iversen, L. L.

doi:10.1111/j.1476-5381.1991.tb12435.x

Cited by 61 publications

(12 citation statements)

References 27 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The slight effect obtained with NKB and senktide could also be explained via other receptors: NK1 and/or NK2. Since the rank order of potency for the NK1 receptor must be SP 1 NKA 1 NKB and for the NK2 receptor NKA 1 NKB 11 SP [17], our results suggest the coexistence of NK1 and NK2 receptors (a hypothesis sustained by the selective antagonism elicited by L-668,169, GR159897, and L-659,877) [4,11,13]. The CGRP antagonist (CGRP8-37) decreases the effect of the injected SP and NKA.…”

Section: Discussionmentioning

confidence: 76%

“…The pED 50 was 12.50 B 0.11 (table 1). The dose-effect curve was displaced to the right principally after pretreatment with 1 nmol/l L-668,169, a NK1 receptor antagonist [11]; the same doses of L-733,060, also a NK1 receptor antagonist, of L659,877 [4], a NK2 receptor antagonist, or of CGRP8-37 [13], the CGRP receptor antagonist, also inhibited the SP-induced response, but to a lesser extent. The pED 50 values obtained are shown in table 1.…”

Section: Resultsmentioning

confidence: 97%

“…Much attention has been focused on the physiological role of peptides in recent years [1,3,4]. A better understanding of the neuropeptide-mediated response will give founded clues to a rational understanding of the physiological mechanisms concerning autoregulation of the vascular tone and transport of substances in retinal vessels.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of Neuropeptides on the Sumatriptan-Disturbed Circulation in the Optic Nerve Head of Rabbits

Gaspar¹,

Ribeiro²,

Cunha-Vaz

et al. 2004

Pharmacology

View full text Add to dashboard Cite

The purpose of this work was to study ‘in vivo’ the vascular responses of retinal vessels of New Zealand white rabbits to substance P (SP), neurokinin A (NKA), neurokinin B (NKB), senktide, capsaicin (CAPS), and calcitonin gene related peptide (CGRP) before and after selective antagonist administration. We examined the effects of these neuropeptides on the normal circulation in the optic nerve head of the rabbit. Drugs were injected via pars plana through a micropipette system. Ten minutes before perivascular injection of 10 nmol/l sumatriptan (to contract the vessel), a selective antagonist or its solvent was administered. Then, cumulative injection of the agonist was performed. The other eye was used as control. Direct measurement of retinal arteriole diameters was performed using digital angiography. The quantification of the relaxing effect is expressed as percentage related to the precontracted vascular diameter. Microinjection of SP (NK1 receptor agonist) up to 10 nmol/l induced a dose-dependent arteriolar dilating effect [E_max (mean ± SEM) 21.3 ± 2.3%]. After the perivascular preinjection of 1 nmol/l L-668,169 or 1 nmol/l L-733,060 (NK1 receptor antagonists), the SP dose-response curve was shifted to the right. The same results were obtained with NKA (NK2 receptor agonist) which induced the most potent effect of all neuropeptides (E_max 53.3±2.5%). The NK2 receptor antagonists L-659,877 and GR 159897 (1 nmol/l) strongly inhibited this arteriolar vasodilation. As for CGRP, doses up to 10 nmol/l induced a marked vasodilation (E_max 41.1±0.4%) which decreased after microinjection of the selective antagonist CGRP8-37. The NK3 receptor agonists (senktide and NKB) showed a minor vasodilating effect (E_max 5.1±1.2 and 8.0±0.9%, respectively). On the contrary, CAPS showed a marked dose-dependent vasodilating effect (E_max 43.2±2.9%), antagonized by the tachykinin receptor antagonists and CGRP8-37. These results suggest, for the first time, the presence of NK1, NK2, and CGRP receptors on the retinal arteriolar wall of the rabbit.

show abstract

Section: Discussionmentioning

confidence: 76%

Section: Resultsmentioning

confidence: 97%

See 1 more Smart Citation

Effects of Neuropeptides on the Sumatriptan-Disturbed Circulation in the Optic Nerve Head of Rabbits

Gaspar¹,

Ribeiro²,

Cunha-Vaz

et al. 2004

Pharmacology

View full text Add to dashboard Cite

show abstract

“…TKs play an exclusively motor role in vas deferens of rat either directly contracting and/or potentiating neurally-mediated contractions (Fournier et al, 1980;Growcott et al, 1982;Lee et al, 1982;Hunter and Maggio, 1984;Kimura et al, 1984;Holzer-Petsche et al, 1985;Osakada et al, 1986;Rovero et al, 1989;McKnight et al, 1991;Miranda et al, 1991;Maggi et al, 1992b;Morimoto et al, 1992b;Williams et al, 1993;Hosoki et al, 1998). This is also the case for guinea-pig (Sjostrand and Swedin, 1968;von Euler and Hedqvist, 1974;Zetler and Kampmann, 1979;Growcott et al, 1982;Stjernquist et al, 1983;Rovero et al, 1989;Hall and Morton, 1991a,b;Patacchini et al, 1992;Anthes et al, 2002), mouse (Blackwell et al, 1978;Segawa et al, 1978;Parlani et al, 1995) and rabbit (Stjernquist et al, 1983;Maggi et al, 1992a).…”

Section: Vas Deferensmentioning

confidence: 77%

Tachykinins and tachykinin receptors: effects in the genitourinary tract

et al. 2005

View full text Add to dashboard Cite

“…In the present study, we tried to characterize the pharmacological nature of tachykinin receptors involved in the contractile response of the isolated rabbit sphincter muscle to endogenous tachykinins released during ETS by using selective NK,-receptor antagonists, spantide and L-668,169 (16), and a selective NK2-receptor antagonist, L-659,877 (17,18). Some of this work has been presented at the International Symposium on "SP and Related Pep tides", held in Shizuoka, Japan, in November, 1992.…”

mentioning

confidence: 99%

Pharmacological Profiles of Muscarinic Receptors in the Longitudinal Smooth Muscle of Guinea Pig Ileum

Kunitomo

Imaizumi

Sameshima

et al. 1993

Japanese Journal of Pharmacology

View full text Add to dashboard Cite

ABSTRACT-We characterized the pharmacological nature of the tachykinin receptor subtype mediating the contractile response to electrical transmural stimulation (ETS) in the isolated rabbit iris sphincter muscle preparation by using selective NK,-receptor antagonists, spantide and L-668,169, and a selective NK2-recep tor antagonist, L-659,877. ETS caused a biphasic contraction in this preparation: a rapidly developing cholinergic component followed by a slowly decaying tachykininergic component. The tachykininergic contractile response to ETS was effectively attenuated by spantide and L-668,169, but only slightly by L 659,877, indicating that the tachykinin receptors mediating ETS-induced contraction are of the NK, type. In the same preparation, the contractile activity of substance P (SP) was slightly more potent than that of neurokinin A (NKA). Unlike in other tissues rich in NK,-receptor subtypes, spantide and L-668,169 an tagonized the contractile response to NKA more effectively than that to SP, and the reverse was observed for L-659,877. These results strongly suggest that the tachykininergic contraction induced by ETS in the rab bit iris sphincter preparation is mediated by NK,-receptors which are activated by endogenously released NKA.

show abstract

Pharmacological specificity of novel, synthetic, cyclic peptides as antagonists at tachykinin receptors

Cited by 61 publications

References 27 publications

Effects of Neuropeptides on the Sumatriptan-Disturbed Circulation in the Optic Nerve Head of Rabbits

Effects of Neuropeptides on the Sumatriptan-Disturbed Circulation in the Optic Nerve Head of Rabbits

Tachykinins and tachykinin receptors: effects in the genitourinary tract

Pharmacological Profiles of Muscarinic Receptors in the Longitudinal Smooth Muscle of Guinea Pig Ileum

Contact Info

Product

Resources

About