[pGlu6, Pro9]SP6-11, a selective agonist for the substance P P-receptor subtype

1986 ◽  
Vol 29 (7) ◽  
pp. 1284-1288 ◽  
Author(s):  
Ralph Laufer ◽  
Chaim Gilon ◽  
Michael Chorev ◽  
Zvi Selinger
Keyword(s):  
Substance P ◽  
Receptor Subtype ◽  
Selective Agonist

Plasma extravasation induced by neurokinins in conscious rats: receptor characterization with agonists and antagonists

1993 ◽  
Vol 71 (3-4) ◽  
pp. 217-221 ◽  
Author(s):  
Mauro Nicolau ◽  
Martin G. Sirois ◽  
Michel Bui ◽  
Gérard E. Plante ◽  
Pierre Sirois ◽  
...  
Keyword(s):  
Substance P ◽  
Urinary Bladder ◽  
Vascular Permeability ◽  
Blue Dye ◽  
Receptor Subtype ◽  
Plasma Extravasation ◽  
Functional Sites ◽  
Conscious Rats ◽  
Selective Antagonists ◽  
Selective Agonists

The purpose of the present experiments was to study the effects of various neurokinin related peptides, such as substance P, [βAla8]NKA(4–10), and [MePhe7]NKB, which are selective for NK-1, NK-2, and NK-3 functional sites, respectively, to induce plasma extravasation in rats and the effectiveness of RP 67580 and CP-96,345 (two nonpeptide NK-1 receptor selective antagonists) and SR 48968 (a nonpeptide NK-2 receptor selective antagonist) to prevent such an effect. Bolus intravenous injection of substance P (1.0 nmol/kg) into conscious rats induced extravasation of Evans blue dye (EB), a selective marker of albumin vascular permeability, in the duodenum, the stomach, the pancreas, and the urinary bladder by 50, 40, 58, and 312%, respectively; a slight increment occurred also in the ileum and the kidney but was not significant. [βAla8]NKA(4–10) (1.0 nmol/kg) increased EB extravasation in the stomach and the urinary bladder by 52 and 99%, respectively, while [MePhe7]NKB (1.0 nmol/kg) did the same in the stomach, the ileum, and the urinary bladder by 58, 50, and 79%. Pretreatment with RP 67580 (250 nmol/kg) blocked the albumin extravasation mediated by substance P in the duodenum, the pancreas, and the urinary bladder by 100, 100, and 78%, respectively. CP-96,345 (250 nmol/kg) also inhibited EB extravasation mediated by substance P in the duodenum and the pancreas by 100 and 100%, respectively, but was ineffective in the urinary bladder. Neither RP 67580 nor CP-96,345 prevented the substance P mediated extravasation in the stomach. RP 67580 and CP-96,345 did not antagonize the effects of NK-2 and NK-3 selective agonists. SR 48968 (500 nmol/kg) was inactive against substance P as well as against the NK-2 or NK-3 selective agonists. RP 67580 (250 nmol/kg), CP-96,345 (250 nmol/kg), and SR 48968 (500 nmol/kg) per se did not induce any plasma extravasation, except in the urinary bladder, where CP-96,345 and SR 48968 increased EB concentrations in the tissue. These results suggest that the effects of neurokinins on vascular permeability vary from one tissue to another. The blockade of substance P by the NK-1 receptor selective antagonists, RP 67580 and CP-96,345, suggests that NK-1 receptors play an important role in the plasma extravasation induced by substance P. However, the effects of NK-2 and NK-3 receptor selective agonists appear to be independent of activation of NK-1 receptors since they are not blocked by RP 67580 or CP-96,345. Furthermore, because the effect of [βAla8]NKA(4–10), the NK-2 selective agonist, was not abolished by SR 48968, it is suggested that it might be mediated by the NK-2 receptor subtype NK-2B, which is less sensitive to SR 48968 than is NK-2A. The contribution of NK-3 receptors to plasma extravasation could not be adequately demonstrated in the present study because NK-3 antagonists sufficiently active in vivo are not available.Key words: neurokinins, RP 67580, CP-96,345, SR 48968, vascular permeability.

scholarly journals Pharmacological characterization of a selective agonist for bombesin receptor subtype-3

2009 ◽  
Vol 387 (2) ◽  
pp. 283-288 ◽  
Author(s):  
Li Zhang ◽  
Hans-Peter Nothacker ◽  
Zhiwei Wang ◽  
Laura M. Bohn ◽  
Olivier Civelli
Keyword(s):  
Receptor Subtype ◽  
Pharmacological Characterization ◽  
Selective Agonist ◽  
Bombesin Receptor ◽  
Subtype 3

Receptors for substance P on isolated intestinal smooth muscle cells of the guinea pig

1987 ◽  
Vol 253 (5) ◽  
pp. G666-G672
Author(s):  
J. C. Souquet ◽  
K. N. Bitar ◽  
J. R. Grider ◽  
G. M. Makhlouf
Keyword(s):  
Smooth Muscle ◽  
Substance P ◽  
Guinea Pig ◽  
Smooth Muscle Cells ◽  
Binding Sites ◽  
Specific Binding ◽  
Muscle Cells ◽  
Receptor Subtype ◽  
Longitudinal Muscle Layer ◽  
Substance K

Two radioligands, 125I-labeled substance P (125I-SP) and 125I-labeled substance K (125I-SK), were used to characterize the kinetics and stoichiometry of binding of mammalian tachykinins [substance P (SP), substance K (SK), and neuromedin K (NK)] to smooth muscle cells isolated from the longitudinal muscle layer of guinea pig intestine. Specific binding of 125I-SP and 125I-SK was rapid, saturable, reversible, and temperature dependent. Binding attained 63-70% of steady-state binding within 1 min, coincidentally with the time of optimal contraction. The order of potency with which mammalian tachykinins and the SP antagonist, [D-Pro2, D-Trp7,9]SP, inhibited the binding of both radioligands was identical: SP greater than SK greater than NK greater than [D-Pro2, D-Trp7,9]SP, implying preferential interaction with a site that had highest affinity for SP. SK was 2-3 times, NK 3-4 times, and [D-Pro2, D-Trp7,9]SP 7-23 times less potent than SP (IC50 0.36 nM). Except for NK, the order of potency was similar to that for contraction of isolated muscle cells. The existence of binding sites with even higher affinity was suggested by the ability of muscle cells to contract in response to concentrations as low as 10(-13) M. These binding sites were not detectable at the concentration of radioligands used. It was concluded that a SP receptor is the only tachykinin receptor subtype present on intestinal muscle cells of the guinea pig.

Synthesis, biological activity, and conformational analysis of [pGlu6, N-MePhe8, Aib9] substance P (6-11): A selective agonist for the NK-3 receptor

Biopolymers ◽  
1993 ◽  
Vol 33 (6) ◽  
pp. 915-926 ◽  
Author(s):  
M. Tallon ◽  
D. Ron ◽  
D. Halle ◽  
P. Amodeo ◽  
G. Saviano ◽  
...  
Keyword(s):  
Biological Activity ◽  
Substance P ◽  
Conformational Analysis ◽  
Selective Agonist

scholarly journals Tachykinins (Substance P, Neurokinin A, Neuropeptide K, and Neurokinin B) in the Cerebral Circulation: Vasomotor Responses in vitro and in situ

1991 ◽  
Vol 11 (4) ◽  
pp. 567-575 ◽  
Author(s):  
I. Jansen ◽  
C. Alafaci ◽  
J. McCulloch ◽  
R. Uddman ◽  
L. Edvinsson
Keyword(s):  
Substance P ◽  
Guinea Pig ◽  
Basilar Artery ◽  
Cerebral Arteries ◽  
Receptor Subtype ◽  
Neurokinin A ◽  
Neurokinin B ◽  
Neuropeptide K

The vasomotor responses of tachykinins have been studied in the cerebral vasculature of human, pig, cat, and guinea pig. Substance P (SP), neurokinin A (NKA), neurokinin B (NKB), and neuropeptide K (NPK) induced concentration-dependent relaxations of precontracted cerebral arteries in all species when examined by a sensitive in vitro technique. In addition, the relaxant responses to SP, NKA, and NKB were studied in cat pial arterioles by peptide microapplication in situ. In human pial vessels, the order of relaxant potency was SP > NKB > NKA > NPK; in the pig middle cerebral artery, there was no difference in potency between the tachykinins; in the cat middle cerebral artery, SP = NKB > NKA = NPK; and in the guinea pig basilar artery, SP » NPK = NKA > NKB. Responses induced by SP, NKA, and NKB in the cat were comparable in vitro and in situ. Removal of the endothelium abolished relaxation induced by all four tachykinins. The relaxant responses of guinea pig basilar arteries to SP, NKA, and NPK were competitively antagonized by the SP antagonist Spantide. However, Spantide lowered the Imax of the NKB concentration–response curve without any rightward shift, suggesting action at a different site than the other tachykinins. In the guinea pig basilar artery, the relaxation seems to be exerted via a NK-1 receptor subtype while the receptor subtype is more unclear in cerebral arteries from human, cat, and pig. It is concluded that relaxations induced by SP, NKA, NKB, and NPK are dependent on the endothelium, and are antagonized either competitively or non-competitively by the SP antagonist Spantide. The origin of tachykinins acting through the endothelium is discussed.

SC-53116: the first selective agonist at the newly identified serotonin 5-HT4 receptor subtype

1992 ◽  
Vol 35 (8) ◽  
pp. 1486-1489 ◽  
Author(s):  
Daniel L. Flynn ◽  
Daniel L. Zabrowski ◽  
Daniel P. Becker ◽  
Roger Nosal ◽  
Clara I. Villamil ◽  
...  
Keyword(s):  
Receptor Subtype ◽  
Selective Agonist ◽  
Sc 53116
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