Cardiovascular effects of amphibian and mammalian tachykinins in the toad, Bufo marinus

Courtice, Gillian P.; Burcher, Elizabeth; Carlo-Stella, R.; Conlon, J. Michael

doi:10.1016/0143-4179(93)90082-l

Cited by 16 publications

(12 citation statements)

References 19 publications

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“…Nonpeptide antagonists, highly potent in mammals, were ineffective as binding competitors and in inhibiting contractile and cardiovascular responses to bufokinin, ranakinin and SP (this study; Courtice et al 1993;Burcher and Warner 1998). The lack of effectiveness of these selective antagonists (which do not chemically resemble the tachykinins) provides support for the theory that antagonists do not necessary interact at the same binding domain as agonists (Schwartz et al 1995).…”

Section: Discussionsupporting

confidence: 61%

Pharmacological and biochemical investigation of receptors for the toad gut tachykinin peptide, bufokinin, in its species of origin

Liu

Warner

Conlon

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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This is the first report of the development of a new radioligand [125I]Bolton-Hunter bufokinin ([125I]BH-bufokinin) and its use in the characterisation of tachykinin receptors in the small intestine of the cane toad, Bufo matrinus. The binding of [125I]BH-bufokinin to toad intestinal membranes was rapid, saturable, of high affinity and to a single population of binding sites with KD 0.57 nM and Bmax 3.1 fmol mg wet weight tissue(-1). The rank order of affinity of tachykinins to compete for [125I]-BH bufokinin binding revealed similarities with that of the mammalian NK1 receptor, being bufokinin (IC50, 1.7 nM)>physalaemin (6.7 nM)>substance P (SP, 10.7 nM)> or =neuropeptide gamma (NPgamma, 12.4 nM)> or =kassinin (17.8 nM)>scyliorhinin I (35.3 nM)> or =eledoisin (40.6 nM)> or =carassin (43.2 nM)> or =neurokinin A (NKA, 57.8 nM)> or =neurokinin B (NKB, 77.5 nM)>scyliorhinin II (338 nM). The mammalian NK3-selective agonist senktide was a very weak competitor. The radioligand [125I]neurokinin A showed no specific binding to toad intestinal membranes. In the toad isolated small intestine, the maximum contractile response to bufokinin was over 150% greater than that to acetylcholine in longitudinal muscle, whereas responses to bufokinin and acetylcholine were similar in circular muscle. Bufokinin was the most potent agonist (EC501 0.34 nM) and produced a long-lasting contraction. Other tachykinins such as physalaemin, SP and kassinin were also potent contractile agents. The potency values of mammalian and amphibian tachykinins derived from functional studies (pD2) correlated significantly with those from binding assays (pKi). The data for fish and molluscan tachykinins, however, showed poor correlation. Contractions to bufokinin and SP were unaffected by atropine, indomethacin and tetrodotoxin. The highly selective NK1 receptor antagonists CP 99994, GR 82334 and RP 67580 were ineffective in both binding and functional studies. Bufokinin increased inositol monophosphate formation in a concentration-dependent manner with an EC50 value of 10.7 nM, suggesting that the tachykinin receptor may be coupled to phosphoinositol hydrolysis. In summary, this study provides evidence for a high-affinity, bufokinin-preferring, NK1-like tachykinin receptor in the toad small intestine. This is probably not the receptor which mediates contraction to carassin, scyliorhinin II and eledoisin. The study also provides evidence that bufokinin and its receptor play an important physiological role in regulating intestinal motility.

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Section: Discussionsupporting

confidence: 61%

Pharmacological and biochemical investigation of receptors for the toad gut tachykinin peptide, bufokinin, in its species of origin

Liu

Warner

Conlon

et al. 1999

Naunyn-Schmiedeberg's Arch Pharmacol

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“…1, SP; 2, neuropeptide γ; 3, NKA; 4, [Sar 9 ]SP; 5, neurokinin B; 6, [Sar 9 ,Met(O 2 ) 11 ]SP; 7, [Lys 5 ,MeLeu 9 ,Nle 10 ] NKA(4-10); 8, senktide; 9, SP(5-11); 10, SP(6-11); 11, SP(4-11); 12, SP(7-11); 13, ranakinin; 14, scyliorhinin II; 15, physalaemin; 16, scyliorhinin I; 17, carassin; 18, eledoisin. For scyliorhinin II and SP(5-11), the high affinity pIC 50 value has been used presumably be ranakinin (Table 1), which was even more potent than SP in lowering blood pressure in the toad (Courtice et al 1993). As expected, this peptide was a potent binding competitor in toad intestinal membranes, as well as previously reported, in rat submandibular gland (O´Harte et al 1991;Badgery-Parker et al 1993).…”

Section: Discussionsupporting

confidence: 53%

“…Thus the lack of effectiveness of non-peptide antagonists in the present study is not surprising. Our previous study in the anaesthetised toad found that ranakinin and SP were potent vasodepressor agents, but were unaffected by CP 96345 (Courtice et al 1993). These results indicate that the receptor regions corresponding to antagonist binding domains in mammals have not been conserved during evolution.…”

Section: Discussionmentioning

confidence: 80%

“…SP is able to contract the isolated intestine (Osborne and Campbell 1986) and splanchnic nerve stimulation and capsaicin induce contraction which is blocked by capsaicin pretreatment, indicating the release of a sensory neuropeptide which may be a tachykinin (Osborne and Campbell 1986). SP and other tachykinins, including the frog peptide ranakinin, are potent vasodepressors in the toad, although the nonpeptide NK-1 receptor antagonist CP 96345 was inactive against SP in this species (Courtice et al 1993). …”

Section: Introductionmentioning

confidence: 99%

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Tachykinin receptors in the small intestine of the cane toad (Bufo marinus): a radioligand binding and functional study

Burcher

Warner

1998

Naunyn-Schmiedeberg's Arch Pharmacol

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In this study, we have used radioligand binding and functional techniques to investigate tachykinin receptors in the small intestine of the cane toad Bufo marinus. The radioligand [125I]Bolton-Hunter [Sar9,Met(O2)11]substance P (selective at mammalian NK-1 receptors) showed no specific binding. Specific binding of [125I]Bolton-Hunter substance P ([125I]BHSP) was saturable, of high affinity (Kd 0.3 nM) and was inhibited by SP (IC50 0.64 nM) > ranakinin approximately neurokinin A (NKA) > or = SP(5-11) > or = neuropeptide gamma > or = scyliorhinin II > scyliorhinin I > or = [Sar9]-SP > or = neurokinin B approximately physalaemin approximately carassin >> SP(7-11) approximately eledoisin > or = SP(4-11) approximately SP(6-11). Binding was also inhibited by Gpp[NH]p > or = GTPgammaS > App[NH]p, indicating a G-protein coupled receptor. The order of potency of tachykinins and analogues in contracting the isolated lower small intestine was carassin (EC50 1.4 nM) > eledoisin approximately SP > or = physalaemin > or = ranakinin > SP(6-11) > scyliorhinin II > or = neuropeptide gamma > neurokinin B approximately NKA approximately scyliorhinin I > or = SP(4-11) > or = SP(5-11) > [Sar9]SP > SP(7-11). In both studies, the selective mammalian NK-1, NK-2 and NK-3 receptor agonists [Sar9,Met(O2)11]SP, [Lys5,Me-Leu9,Nle10]NKA(4-10) and senktide were weak or ineffective. There was a strong positive correlation between the pD2 and pIC50 values for mammalian tachykinins and analogues (r = 0.907), but not for the non-mammalian tachykinins, which were all full agonists but variable binding competitors. [Sar9,Met(O2)11]-SP(pD2 5.7) was approximately 25-fold less potent as an agonist than [Sar9]SP, which was itself 25-fold weaker than SP. Responses to SP were significantly reduced (n = 8, P<0.001) by the antagonist [D-Arg1,D-Trp7,9,Leu11]-SP (spantide; 1 microM). Highly selective NK-1 receptor antagonists including CP 99994 and GR 82334 (both 1 microM) were ineffective in both functional and binding studies. Tetrodotoxin (1 microM) did not inhibit contractile responses to SP, NKA and senktide. In summary, this study has shown the presence of one or more tachykinin receptor in the toad intestine. The binding site recognised by [125I]BHSP prefers SP and ranakinin. This toad "NK-1-like receptor" differs from the mammalian NK-1 receptor in having a low affinity for all mammalian NK-1 selective ligands, including antagonists. For some non-mammalian peptides, their high potency as contractile agonists relative to their poor binding affinity suggests the existence of other tachykinin receptors in the toad small intestine.

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“…Several in vivo studies show that mammalian SP decreases vascular resistance in most mammals, in the crocodile, Crocodylus porosus, in the toad, Bufo marinus, and, notably, in the coeliac vascular bed of cod (e.g., Pernow 1983;Jensen et al 1991;Courtice et al 1993;Karila et al 1995;Lundgaard et al 1997). In contrast, mammalian SP increased coeliac vascular resistance in the common dogfish and in lungfish, and native SP produced a slight increase in blood pressure (Waugh et al 1993;Holmgren et al 1994).…”

Section: Discussionmentioning

confidence: 97%

Cod CGRP and tachykinins in coeliac artery innervation of the Atlantic cod, Gadus morhua: presence and vasoactivity

Shahbazi

Holmgren

Jensen

2008

Fish Physiol Biochem

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The presence and vasoactive effects of native calcitonin gene-related peptide (CGRP), substance P (SP), and neurokinin A (NKA) were studied on isolated small branches of the coeliac artery from Atlantic cod, Gadus morhua, using immunohistochemistry and myograph recordings, respectively. Immunohistochemistry revealed nerve fibers containing CGRP- and SP/NKA-like material running along the wall of the arteries. CGRP induced vasorelaxation of precontracted arteries with a pD(2) value of 8.54 +/- 0.17. Relaxation to CGRP (10(-8) M) was unaffected by L-NAME (3 x 10(-4) M) and indomethacin (10(-6) M) suggesting no involvement of nitric oxide or prostaglandins in the CGRP-induced relaxation. SP and NKA (from 10(-10) to 3 x 10(-7) M) contracted the unstimulated arteries at concentrations from 10(-8) M and above in 42% and 33%, respectively, of the vessels. It is concluded that the innervation of the cod celiac artery includes nerves expressing CGRP-like and tachykinin-like material, and that a vasodilatory response to CGRP is highly conserved amongst vertebrates while the response to tachykinins is more variable.

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Cardiovascular effects of amphibian and mammalian tachykinins in the toad, Bufo marinus

Cited by 16 publications

References 19 publications

Pharmacological and biochemical investigation of receptors for the toad gut tachykinin peptide, bufokinin, in its species of origin

Pharmacological and biochemical investigation of receptors for the toad gut tachykinin peptide, bufokinin, in its species of origin

Tachykinin receptors in the small intestine of the cane toad (Bufo marinus): a radioligand binding and functional study

Cod CGRP and tachykinins in coeliac artery innervation of the Atlantic cod, Gadus morhua: presence and vasoactivity

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