Molecular characterization and functional expression of a substance P receptor from the sympathetic ganglion of Rana catesbeiana

Simmons, Mark A.; Brodbeck, Robbin; Karpitskiy, Vladimir; Schneider, Carla R.; Neff, Don; Krause, James E.

doi:10.1016/s0306-4522(97)00027-4

Cited by 17 publications

(14 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, immunocytochemical techniques have identified SP-like molecules in amphibian visual structures that correspond well with the distribution of SP in homologous regions of the mammalian brain (Andersen et al, 1992). Furthermore, these SP-like molecules act through receptors characterized as having the features of an SP receptor (O'Harte et al, 1991;Simmons et al, 1997).…”

Section: Introductionmentioning

confidence: 86%

Distribution and regulation of substance P‐related peptide in the frog visual system

Debski

2001

Microscopy Res & Technique

View full text Add to dashboard Cite

Modulation of visual signal activity has consequences for both signal processing and for activity-dependent structuring mechanisms. Among the neuromodulatory agents found in visual areas are substance P (SP)-related peptides. This article reviews what is known about these substances in the amphibian retina and optic tectum with special emphasis on the leopard frog, Rana pipiens. It is found that the distribution of these SP-related peptides is remarkably similar to that seen in mammals. This suggests that study of model amphibian systems may significantly enhance our understanding of how neuropeptides contribute to visual system function and organization.

show abstract

Section: Introductionmentioning

confidence: 86%

Distribution and regulation of substance P‐related peptide in the frog visual system

Debski

2001

Microscopy Res & Technique

View full text Add to dashboard Cite

show abstract

“…As these peptides were originally isolated from bullfrog (Kangawa et al, 1993), their actions on neurons isolated from bullfrog sympathetic ganglia have been examined. These neurons express the bullfrog SP receptor, which exhibits a 69% overall amino acid sequence identity with the rat and human NK 1 receptors, with the amino acid residues in regions of the receptor known to be important for SP binding being even more highly conserved (Simmons et al, 1997). When applied to these neurons, SP results in a concentration-dependent inhibition of a time-and voltage-sensitive K ϩ current termed I M (Simmons et al, 1994).…”

Section: Concentration-response Curve For Inhibition Of the M-type Pomentioning

confidence: 99%

Functional Selectivity of NK₁Receptor Signaling: Peptide Agonists Can Preferentially Produce Receptor Activation or Desensitization

Simmons¹

2006

J Pharmacol Exp Ther

View full text Add to dashboard Cite

A cascade of events follows binding of an agonist ligand to the tachykinin NK 1 receptor. These events include activation of multiple signal transduction pathways as well as cellular modulation of receptor function by the process of desensitization. This study examines the differences in the abilities of naturally occurring peptide agonist ligands of the tachykinin NK 1 receptor to preferentially direct signaling through the receptor to produce signal activation versus receptor desensitization. The differential effects of tachykinin peptides with respect to ligand competition binding, receptor-G protein coupling, intracellular Ca 2ϩ elevations, and receptor desensitization have been measured. In relation to its potency in competition binding studies, substance P produces desensitization at lower concentrations, whereas higher concentrations are required to elicit a Ca 2ϩ response. In contrast to this, a related peptide, ranatachykinin C, is more effective at activating a Ca 2ϩ response relative to its ability to produce desensitization. This difference in functional selectivity is conserved for an amphibian and two mammalian ortholog tachykinin receptors. The present study demonstrates that peptide agonist ligands of NK 1 receptors can preferentially produce signal activation or desensitization.Over the years, the interactions of ligands with receptors have been classified as agonist interactions or antagonist interactions. Recently, it has become clear that a multitude of effects can follow binding of a ligand to a receptor (Kenakin, 2002(Kenakin, , 2003. These effects involve activation of multiple signal transduction pathways as well as cellular modulation of receptor function.One way that receptor function is modulated is by the process of desensitization. Desensitization occurs when the response to an agonist wanes in the continued presence of that agonist. Studies from our lab (Perrine et al., 2000) and from other labs (Vigna, 2001) have shown that the ability of a tachykinin receptor agonist ligand to produce signal activation and its ability to produce desensitization are not necessarily correlated.Our initial findings in this area showed that four different tachykinin peptides, substance P (SP), ranatachykinin (RTK) A, RTKB, and RTKC, could each activate the signal transduction pathways of the bullfrog SP receptor. For SP and RTKA, the concentrations required to produce desensitization of the receptor were two to four times less than the concentrations required to produce receptor activation. In contrast to this, the concentrations of RTKB and RTKC that produced desensitization were two times greater than the concentration needed to activate the signal transduction pathway.These data suggested that agonist ligands of the NK 1 receptor may exhibit functional selectivity. That is, agonists with the highest affinity and efficacy to activate a given signal transduction pathway do not also show the greatest degree of desensitization. This possibility seems particularly conceivable with respect to pep...

show abstract

“…Total RNA from intestinal smooth muscle and brain was reversetranscribed and PCR amplified using TM-2 and TM-7 primers (Table 1), which were derived from the conserved TM II and VII regions of the bullfrog NK 1-like receptor cDNA sequence (32). cDNA was created and amplified as per the manufacturer's instructions (Access RT-PCR System, Promega).…”

Section: Amplification Of Partial Cdnas By Rt-pcrmentioning

confidence: 99%

“…NK 1 -like receptors cloned from chicken (GenBank AF131057) and from fugufish Fugu rubripes (GenBank AY327862) show 78 and 65% identity, respectively, at the amino acid level, to their human counterpart. In the bullfrog Rana catesbeiana, an SP-preferring receptor isolated from sympathetic ganglion exhibits 70% identity to mammalian NK 1 receptors (32). Across these diverse vertebrate species, cytoplasmic loop 1 and transmembrane (TM) regions II and VII are highly conserved (92-100% identity), whereas the extracellular NH 2 terminus and extracellular loops 2 and 3 are the least conserved regions (15-61% identity).…”

mentioning

confidence: 99%

Molecular identification and characterization of three isoforms of tachykinin NK₁-like receptors in the cane toadBufo marinus

Liu

Markus²,

Vandenberg³

et al. 2004

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

. Molecular identification and characterization of three isoforms of tachykinin NK1-like receptors in the cane toad Bufo marinus. Am J Physiol Regul Integr Comp Physiol 287: R575-R585, 2004. First published May 20, 2004 10.1152/ajpregu.00051.2004.-The tachykinin peptide bufokinin, isolated from the cane toad intestine, is important in intestinal and cardiovascular regulation in the toad. In this study, three tachykinin NK1-like receptor isoforms, bNK1-A, bNK1-B, and bNK1-C, encoding proteins of 309, 390, and 371 amino acids, respectively, were cloned from the toad brain and intestine. These isoforms differ only at the intracellular COOH terminus. The bNK1-A and bNK1-B isoforms are similar to the truncated and full-length forms of the mammalian NK1 receptor, whereas bNK1-C is unique and does not correspond to any previously described receptor. RT-PCR studies demonstrated that three isoform transcripts are widely distributed in the toad with high expression in gut, spinal cord, brain, lung, and skeletal muscle. When expressed in COS-7 cells, bufokinin showed similar high affinity (IC50 0.6 -0.8 nM) in competing for 125 I-labeled Bolton-Hunter bufokinin binding at all receptors, but the binding affinities of substance P (SP) and neurokinin A (NKA) were very different at each isoform. When expressed in Xenopus oocytes, the truncated isoform, bNK1-A, was inactive, whereas bNK1-B and bNK1-C produced changes in chloride current when stimulated by tachykinins (minimum concentrations: bufokinin, 0.1 nM; SP, 1 nM; and NKA, 10 nM). A marked desensitization of the response was seen to subsequent applications of tachykinins, as experienced by the mammalian NK1 receptor. In summary, our study describing three isoforms of NK1-like receptor from the toad suggests that the alternative splicing of NK1 receptor is a physiologically conserved mechanism and raises a fundamental question as to the physiological role of each isoform. bufokinin; tachykinin receptors; sequencing and cloning; Xenopus oocyte expression; amphibian TACHYKININS are multifunctional brain, gut, and skin peptides that possess a variety of biological roles in the central and peripheral nervous systems as well as in the cardiovascular and immune systems. Their actions include vasodilatation, plasma extravasation, smooth muscle contraction, secretion, neuronal excitation, and processing of sensory information; in addition, they have extensive proinflammatory properties (13). In mammals, substance P (SP), neurokinin A (NKA), and neurokinin B are the best known members of this family and act preferentially through tachykinin NK 1 , NK 2 , and NK 3 receptors, respectively (27). Most recently, several new mammalian tachykinins (hemokinin and the endokinins) have been isolated from nonneural tissues (27). The tachykinin family is phylogenetically ancient and has been well conserved throughout evolution, with numerous structurally related tachykinins isolated from a wide range of vertebrates and invertebrates (15). The amino acid sequences of tachykinins from mammals,...

show abstract

Molecular characterization and functional expression of a substance P receptor from the sympathetic ganglion of Rana catesbeiana

Cited by 17 publications

References 43 publications

Distribution and regulation of substance P‐related peptide in the frog visual system

Distribution and regulation of substance P‐related peptide in the frog visual system

Functional Selectivity of NK₁Receptor Signaling: Peptide Agonists Can Preferentially Produce Receptor Activation or Desensitization

Molecular identification and characterization of three isoforms of tachykinin NK₁-like receptors in the cane toadBufo marinus

Contact Info

Product

Resources

About

Molecular characterization and functional expression of a substance P receptor from the sympathetic ganglion of Rana catesbeiana

Cited by 17 publications

References 43 publications

Distribution and regulation of substance P‐related peptide in the frog visual system

Distribution and regulation of substance P‐related peptide in the frog visual system

Functional Selectivity of NK1Receptor Signaling: Peptide Agonists Can Preferentially Produce Receptor Activation or Desensitization

Molecular identification and characterization of three isoforms of tachykinin NK1-like receptors in the cane toadBufo marinus

Contact Info

Product

Resources

About

Functional Selectivity of NK₁Receptor Signaling: Peptide Agonists Can Preferentially Produce Receptor Activation or Desensitization

Molecular identification and characterization of three isoforms of tachykinin NK₁-like receptors in the cane toadBufo marinus