Isolation, analysis of structure, synthesis, and biological actions of urotensin I neuropeptides

Lederis, K.; Letter, Anita A.; McMaster, D.; Ichikawa, Tomoyuki; MacCannell, Keith L.; Kobayashi, Yuta; Rivier, Jean; Rivier, Catherine; Vale, Wylie; Fryer, James N.

doi:10.1139/o83-076

Cited by 49 publications

(17 citation statements)

References 14 publications

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“…Although CRF, sauvagine, and urotensin I are equipotent in releasing ACTH, it is important to note that sauvagine and urotensin I are 10-fold more potent than CRF as vasodilator agents (35). Our results are consistent with this, as sauvagine and urotensin I are at least 10-fold more potent than CRF as inducers of intracellular cAMP levels in cells expressing HM-CRF receptor.…”

Section: E-qe--neekkskv--h--v-i-supporting

confidence: 86%

A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle

1995

Proc. Natl. Acad. Sci. U.S.A.

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Corticotropin-releasing factor (CRF) mediates many critical aspects of the physiological response to stress. These effects are elicited by binding to specific highaffinity receptors, which are coupled to guanine nucleotide stimulatory factor (Gs)-response pathways. Recently, a gene encoding a receptor for CRF, expressed in pituitary and the central nervous system (PC-CRF receptor), was isolated and characterized. Here we report the identification and characterization of a second, distinct CRF receptor that is expressed primarily in heart and skeletal muscle and exhibits a specific ligand preference and antagonist sensitivity compared with the PC-CRF receptor. We refer to this second receptor as the heart/muscle (HM)-CRF receptor.Corticotropin-releasing factor (CRF) (1) is a member of a family of peptides from different species that act as agonists of the CRF receptor. These peptides include the frog skin peptide, sauvagine (2), and the teleost fish urophysis peptide, urotensin I (3). CRF is a 41-amino acid hypothalamic neuropeptide that plays a central role in coordinating the communications between endocrine, nervous, and immune systems to achieve homeostasis in response to environmental adversities (4, 5). The peptide was originally characterized in the hypothalamo-hypophyseal system but was later found to be widely distributed throughout the central nervous system (CNS), where it appeared to function as a neurotransmitter or neuromodulator (6). In the CNS, CRF initiates the hypothalamic-pituitary-adrenal axis by stimulating the release of adrenocorticotropin (ACTH) and ,B-endorphin from the anterior pituitary. ACTH stimulates adrenal cortex to secrete corticosteroids that, in turn, elicit a wide range of biological responses and exert negative feedback on the hypothalamus and pituitary (4, 5, 7). Both sauvagine and urotensin I have been shown to stimulate the hypothalamic-pituitary-adrenal axis after i.v. administration (8). Intracerebroventricular administration of CRF provokes stress-like responses including activation of the sympathetic nervous system, resulting in an elevation of plasma epinephrine, norepinephrine, and glucose, which results in increased heart rate and mean arterial blood pressure (9, 10). Outside the CNS, CRF immunoreactivity is detectable in multiple peripheral organs, including placenta, adrenal medulla, pancreas, lung, stomach, duodenum, and liver (4, 5). i.v. administration of CRF, sauvagine, and urotensin I has been shown to elicit peripheral systemic responses, including vasodilation (11).CRF functions by binding to a membrane-bound receptor that is coupled to the guanine nucleotide stimulatory factor (G,) signaling protein, resulting in increased intracellular cAMP levels (12,13 (23), and growth hormonereleasing factor ]. The PC-CRF receptor mRNA was found to be most highly expressed in the cerebellum and pituitary and found at lower levels in other brain areas, intestine, and testes. This receptor is undetectable in other tissues examined, including heart and skeletal mus...

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Section: E-qe--neekkskv--h--v-i-supporting

confidence: 86%

A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle

1995

Proc. Natl. Acad. Sci. U.S.A.

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“…CRF is considered to stimulate many of the functions that help the organism survive (such as locomotor activity and catecholamine release) while inhibiting those that might interfere with an effective stress response (such as † IUPAC rules are used for nomenclature of peptides including oneletter codes for amino acids. Abbreviations: Ac, acetyl; ACTH, adrenocorticotropin hormone; Astressin, cyclo (30)(31)(32)(33) feeding and sexual behavior). 8 The actions of CRF are mediated through binding to CRF receptors, several of which have been characterized recently.…”

Section: Introductionmentioning

confidence: 99%

Minimal-Size, Constrained Corticotropin-Releasing Factor Agonists withi−(i+3) Glu−Lys and Lys−Glu Bridges

Rivier

Gulyás

et al. 1998

J. Med. Chem.

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In three earlier publications (Miranda et al. J. Med. Chem. 1994, 37, 1450-1459; 1997, 40, 3651-3658; Gulyas et al. Proc. Natl. Acad. Sci. U.S.A. 1995, 92, 10575-10579) we have hypothesized that covalent constraints such as side-chain-to-side-chain lactam rings would stabilize an alpha-helical conformation shown to be important for the recognition and binding of the CRF C-terminus 30 residues, to CRF receptors. These studies led to the discovery of useful CRF antagonists such as alpha-helical CRF (alpha-hel-CRF) and Astressin both in vitro and in vivo. To test the hypothesis that such lactam rings may also be modulating activation of the receptor when introduced at the N-terminus of CRF, we studied the influence of the successive introduction from residues 4 to 14 of a cyclo(i, i+3)[Lysi-Glu(i+3)] and a cyclo(i,i+3)[Glui-Lys(i+3)] bridge on the in vitro potency of the agonist [Ac-Pro4,dPhe12,Nle21,38]hCRF(4-41) and related compounds. We have also introduced the favored cyclo(Glu30-Lys33) substitution found to be remarkable in several families of antagonists (such as Astressin) and in a number of CRF agonists and investigated the role of residues 4-8 on receptor activation using successive deletions. Earlier studies had shown that in both oCRF and alpha-helical CRF, deletion of residues 1-6, 1-7, and 1-8 led to gradual loss of intrinsic activity (IA) (from 50% IA to <10% IA) resulting in alpha-hel-CRF being a potent competitive antagonist. We show that acetylation of the N-terminus of these fragments generally increases potency by a factor of 2-3 with no influence on IA. While cyclo(30-33)[Ac-Leu8,dPhe12,Nle21, Glu30,Lys33,Nle38]hCRF(8-41) (30) is the shortest reported analogue of CRF to be equipotent to CRF (70% IA), the corresponding linear analogue (31) is 120 times less potent (59% IA). Addition of one amino acid at the N-terminus ¿cyclo(30-33)[Ac-Ser7,dPhe12,Nle21, Glu30,Lys33,Nle38]hCRF(7-41) (28)¿ results in a 5-fold increase in agonist potency and full intrinsic activity (113%). The most favored modifications were also introduced in other members of the CRF family including sauvagine (Sau), urotensin (Utn), urocortin (Ucn), and alpha-hel-CRF. Parallel and consistent results were obtained suggesting that the lactam cyclization at residues 29-32 and 30-33 (for the members of the CRF family with 40 and 41 amino acid residues, respectively) will induce (in the shortened agonists) a structural constraint (alpha-helix) that stabilizes a bioactive conformation similar to that shown in the Astressin family of CRF antagonists and that residue 8 (leucine or isoleucine) bears the sole responsibility for activation of the receptor since deletion of that residue leads to potent antagonists (Gulyas et al. Proc. Natl. Acad.Sci. U.S.A. 1995, 92, 10575-10579).

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“…Recently, the primary structure of UI peptides has been determined (3,4); a close similarity exists among UI, mammalian corticotropin-releasing factors (CRFs) (5-7), and sauvagine, a peptide isolated from the skin of a frog (8). The structural homology of UI with CRF suggests a possible role of UI as a fish CRF, and recent biological experiments support this possibility (9)(10)(11). Characterization of the gene encoding the precursor of UI would help to elucidate the evolutionary relationship of UI to other related peptides.…”

mentioning

confidence: 97%

Cloning and sequence analysis of cDNA encoding urotensin I precursor.

Ichikawa¹,

Deguchi²

1986

Proc. Natl. Acad. Sci. U.S.A.

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The primary structure of the precursor of urotensin I, a neuropeptide hormone from the caudal neurosecretory system of the carp Cyprinus carpio, has been determined by analyzing the nucleotide sequence of cloned DNA complementary to the mRNA encoding it. The precursor consists of 145 amino acid residues and the carboxyl terminus represents the 41-amino acid sequence of urotensin I, preceded by Lys-Arg and followed by Gly-Lys. Sequence homology as well as similar organization of the precursors of urotensin I and mammalian corticotropin-releasing factors suggest that they are evolutionarily related. RNA transfer blot analysis indicates that mRNA encoding the precursor of urotensin I is present only in the spinal cord and not in the brain, intestine, liver, or kidney of the carp.Urotensin I (UI) is one ofthe neuropeptides released from the urophysis, the neurohemal organ of the caudal neurosecretory system of teleosts. UI has potent hypotensive activity in mammals (1), and a relationship between this peptide and osmoregulation has been suggested for fishes (2). Recently, the primary structure of UI peptides has been determined (3, 4); a close similarity exists among UI, mammalian corticotropin-releasing factors (CRFs) (5-7), and sauvagine, a peptide isolated from the skin of a frog (8). The Identification of Carp UI Precursor cDNA. A total of 6000 transformants was screened by colony hybridization using a mixture of 32P-labeled synthetic oligonucleotides, 5' GC-CAT(T,C)TC(A,G,C,T)ATCAT 3', representing all possible cDNA sequences that correspond to the pentapeptide sequence Met-Ile-Glu-Met-Ala, amino acid residues 18-22 of carp UI (Fig. 2a). The probe was 5' end-labeled to a specific activity of 1.2 x 108 cpm/,Rg. The filters were hybridized with the probe for 46 hr at 370C in 0.6 M NaCIV60 mM sodium citrate, pH 7.4)/10x concentrated Denhardt's solution (lx Denhardt's = 0.02% bovine serum albumin/0.02% Ficoll/ 0.02% polyvinylpyrrolidone)/E. coli DNA (100 Ag/ml) and washed twice at 0C for 5 min and twice at 37TC for 20 min in 0.6 M NaCl/60 mM sodium citrate.Nucleotide Sequence Analysis. Plasmids from the positive clones were analyzed by several restriction enzymes. The inserts from the positive clones were subcloned into pUC 18 vector and various deleted plasmids were prepared by the kilosequence method (20) 308The publication costs of this article were defrayed in part by page charge payment. This article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. §1734 solely to indicate this fact.

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Isolation, analysis of structure, synthesis, and biological actions of urotensin I neuropeptides

Cited by 49 publications

References 14 publications

A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle

A sauvagine/corticotropin-releasing factor receptor expressed in heart and skeletal muscle

Minimal-Size, Constrained Corticotropin-Releasing Factor Agonists withi−(i+3) Glu−Lys and Lys−Glu Bridges

Cloning and sequence analysis of cDNA encoding urotensin I precursor.

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