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J M Conlon

Publications and source records attributed to J M Conlon.

At least 235 records · Page 13Linked to original sources
PubMed1989

Isolation and primary structure of the C-peptide of proinsulin from the European eel (Anguilla anguilla).

1. The primary structure of the C-peptide of proinsulin from the European eel has been established as: DVEPLLGFLSPKSGQENEVDDFPYKGQGEL. The peptide was isolated from the extract of eel pancreas in a yield that was approximately equimolar with insulin. A comparison with the predicted structures of C-peptides from other teleost fishes has identified a domain in the central region of the peptide that has been more highly conserved than the rest of the molecule.

Amino Acid Sequence↗
PubMed1989

Quantitation and characterization of peptides from the C-terminal flanking region of rat and bovine preprotachykinins.

Sequence analysis of cDNAs has shown that the biosynthetic precursors of substance P (alpha-, beta-, and gamma-preprotachykinins) contain a common amino acid sequence in the C-terminal flanking region that has not been conserved between species. Antisera have been raised against the synthetic peptide Tyr-Glu-Arg-Ser-Ala-Met-Gln-Asn-Tyr-Glu, which represents rat beta-preprotachykinin-(117-126)-peptide, and used in radioimmunoassays. Antiserum R50 reacted strongly with C-flanking peptides in extracts of rat and bovine tissues whereas antiserum GP-4 reacted only with the rat peptides. The primary structure of the predominant molecular form of preprotachykinin C-flanking peptide in an extract of bovine corpus striatum was established as: Ala-Leu-Asn-Ser-Val5-Ala-Tyr-Glu-Arg-Ser10-Val-Met-Gln-Asp-Tyr1 5-Glu. This sequence represents beta-preprotachykinin-(111-126)-peptide which is equivalent to gamma-preprotachykinin-(96-111)-peptide. A C-flanking peptide with similar chromatographic properties was identified in extracts of rat brain and gut together with a second immunoreactive component that may represent a fragment or a posttranslationally modified variant. A peptide corresponding to the 37-amino-acid residue C-flanking peptide derived from alpha-preprotachykinin was not detected in the extracts as expected from the known low abundance of alpha-preprotachykinin mRNA in rat brain and gut.

Amino Acid Sequence↗
PubMed1989

Characterization of the receptor for glucagon-like peptide-1(7-36)amide on plasma membranes from rat insulinoma-derived cells by covalent cross-linking.

125I-Labelled glucagon-like peptide-1(7-36)amide was cross-linked to a specific binding protein in plasma membranes prepared from RINm5F rat insulinoma-derived cells using disuccinimidyl suberate. Consistent with the presence of a single class of binding site on the surface of intact cells, only a single radiolabelled band at Mr63,000 was identified by SDS-PAGE after solubilization of the ligand-binding protein complex. The band was not observed when 10nM glucagon-like peptide-1(7-36)amide was included in the binding assay, but 1 microM concentrations of glucagon-like peptide-1(1-36)amide, glucagon-like peptide-2 and glucagon did not decrease the intensity of labelling. No change in the mobility of the band was observed under reducing conditions, suggesting that the binding protein in the receptor is not attached to other subunits via disulphide bonds. In control incubations using plasma membranes from pig intestinal epithelial cells, which do not contain specific binding sites for glucagon-like peptide-1(7-36)amide, no cross-linked ligand-binding protein complex was observed.

Adenoma, Islet Cell↗
PubMed1989

Effect of ovarian hormones, pregnancy and lactation on somatostatin and substance P in the alimentary tract of mice.

Immunoreactive somatostatin and substance P were determined in extracts of alimentary tract (stomach to colon) from the following groups of adult female mice: intact control, ovariectomized, ovariectomized and treated with oestradiol (50 micrograms/kg per day) and/or progesterone (2 mg/kg per day) for 30 days, 19-day-pregnant, and 10-day-postpartum lactating. Ovariectomy increased the somatostatin concentration of the stomach (by 52%, P less than 0.05), jejunum (by 116%, P less than 0.01) and caecum (by 114%, P less than 0.01). These effects were partially or totally prevented by the oestradiol and progesterone treatments, especially the oestradiol-progesterone combination, except for an increase (by 126%, P less than 0.01) in gastric somatostatin after treatment with oestradiol alone. Lactation also increased gastric somatostatin (by 108%, P less than 0.001), but the somatostatin concentration of other regions of the alimentary tract (jejunum to colon) was reduced (by 21-55%, P less than 0.05) in pregnant and lactating mice. The concentration of substance P was increased by ovariectomy in stomach (by 69%, P less than 0.01), duodenum (by 84%, P less than 0.05), ileum (by 163%, P less than 0.001) and caecum (by 57%, P less than 0.01). This effect was partially or totally prevented by treatment with progesterone alone and by the oestradiol-progesterone combination, but not by oestradiol alone. Pregnancy and lactation increased gastric substance P by 46% (P less than 0.01) and 61% (P less than 0.001) respectively, but substance P concentrations in other regions of the alimentary tract were not significantly altered.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Effects of growth hormone-releasing hormone on the secretion of islet hormones and on glucose homeostasis in lean and genetically obese-diabetic (ob/ob) mice and normal rats.

The effect of synthetic human growth hormone-releasing hormone(1-40) (hGHRH-40) on the function of the endocrine pancreas and on glucose homeostasis in lean and genetically obese-diabetic (ob/ob) mice and normal rats has been examined. The addition of 1 mumol hGHRH-40/1 to incubated islets from normal lean mice increased insulin release by 90 and 37% at 5.6 and 16.7 mmol glucose/l respectively. Lower concentrations of hGHRH-40 did not affect insulin release. hGHRH-40 (1 mumol/l) increased pancreatic polypeptide release by 50% at 5.6 mmol glucose/l. A range of concentrations of hGHRH-40 (1 nmol/l-1 mumol/l) reduced glucagon release by 42-73% at 5.6 mmol glucose/l, and by 38-70% at 16.7 mmol glucose/l. Somatostatin release was increased (eightfold) by 1 mumol hGHRH-40/1 at 5.6 mmol glucose/1, but at 1 nmol hGHRH-40/1 somatostatin release was reduced (by greater than 50%). At 16.7 mmol glucose/litre 0.01-1 mumol hGHRH-40/1 increased somatostatin release (three- to fourfold), but 1 nmol hGHRH-40/1 produced a reduction of 50%. In vivo, administration of hGHRH-40 (50 micrograms/kg body weight i.p.) to fasted lean and ob/ob mice did not alter basal plasma concentrations of glucose and insulin, or the glucose and insulin responses to a concomitant i.p. glucose challenge. Intravenous injection of hGHRH-40 (20 micrograms/kg body weight) to anaesthetized rats increased plasma concentrations of insulin in the hepatic portal vein. A lower dose of hGHRH-40 (0.2 micrograms/kg) was ineffective, and neither dose of hGHRH-40 altered plasma glucose.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Post-translation processing of neurohormonal peptide precursors in a human medullary thyroid carcinoma.

Determination of the Primary structures of peptides isolated from a human medullary thyroid carcinoma has provided insight into the pathways of post-translational processing of prohormones in the tumour cells. Cleavage of the signal peptide in preprocalcitonin occurs at the Ala25-Ala26 bond. The prohormone is further processed at the site of multiple basic residues to generate procalcitonin-(1-57)-peptide, procalcitonin-(60-91)-peptide (calcitonin), procalcitonin(60-116)-peptide (a C-terminally extended form of calcitonin) and procalcitonin-(96-116)-peptide (Katacalcin). CGRP-I but not CGRP-II, was isolated from the tumour together with a high-Mr form that may represent the unprocessed prohormone. Progastrin-releasing peptide was processed to a mixture of GRP-(1-27)-peptide and GRP-(18-27)-peptide, the latter component arising from proteolytic cleavage at the site of a single arginyl residue.

Calcitonin↗
PubMed1988

Neurotensin and prostaglandin interactions in smooth muscle of the guinea pig stomach.

Neurotensin, xenopsin and neuromedin N had a biphasic effect (initial small relaxation followed by a sustained contraction) on the motility of longitudinal muscle strips from the guinea pig gastric corpus. Kinetensin was without effect. Tetrodotoxin, adrenaline, histamine, 5-hydroxytryptamine, opioid peptides, angiotensin II and antagonists of acetylcholine, and desensitization of the strips to bradykinin did not modify the action of neurotensin. The contraction phase was inhibited in a concentration-dependent manner by indomethacin and acetylsalicylate, demonstrating that this activity of neurotensin was dependent on prostaglandin synthesis. The preparation responded to exogenous prostaglandins E1, E2, F1 alpha and F2 alpha with concentration-dependent contractions. The relaxation phase was abolished by verapamil and apamin, indicating the presence of inhibitory neurotensin receptors on smooth muscle cells that are linked to ionic channels.

Animals↗
PubMed1988

Structural characterization of a high-molecular-mass form of calcitonin [procalcitonin-(60-116)-peptide] and its corresponding N-terminal flanking peptide [procalcitonin-(1-57)-peptide] in a human medullary thyroid carcinoma.

Four peptides derived from procalcitonin were isolated in high yield from an extract of a human medullary thyroid carcinoma. The peptides were identified as procalcitonin-(1-57)-peptide, procalcitonin-(60-91)-peptide (calcitonin), procalcitonin-(60-116)-peptide and procalcitonin-(96-116)-peptide (katacalcin). Determination of the amino acid sequence of procalcitonin-(1-57)-peptide has demonstrated that the Ala25-Ala26 bond in preprocalcitonin is the site of cleavage of the signal peptide. Procalcitonin-(60-116)-peptide represents calcitonin extended from its C-terminus by the sequence Gly-Lys-Lys-Arg-katacalcin, and its formation is indicative of an aberrant pathway of procalcitonin processing in the tumour cells.

Amino Acids↗
PubMed1988

Effects of neurotensin-related peptides on the motility of the guinea pig oesophagus.

Neurotensin, neuromedin N and xenopsin induced a monophasic and concentration-dependent contraction of the intact guinea pig oesophagus but kinetensin was without effect. The responses were completely abolished by tetrodotoxin and atropine but were unaffected by hexamethonium. The maximum response induced by neurotensin was reduced (20-30%) by somatostatin and by dynorphin-(1-13) in a naloxone-reversible manner. Neurotensin did not contract the isolated muscularis mucosae. The effects of neurotensin-related peptides on the motility of the oesophagus are mediated exclusively through the release of acetylcholine.

Animals↗
PubMed1988

Post-translational processing of preprotachykinins. Isolation of protachykinin-(1-37)-peptide from human adrenal-medullary phaeochromocytoma tissue.

The biosynthetic precursors of the mammalian tachykinins, alpha-, beta-and gamma-preprotachykinins, contain a common N-terminal region of 74 amino acids. A polyclonal antiserum was raised against a synthetic peptide representing N-tyrosylated beta-preprotachykinin-(48-56)-peptide as predicted from the nucleotide sequence of cloned DNA complementary to human beta-preprotachykinin mRNA. By using this antiserum in radioimmunoassay, a single immunoreactive peptide was identified in an extract of a human pheochromocytoma that produced substance P and neurokinin A. Partial microsequencing and determination of the amino acid composition of the peptide indicated identity with preprotachykinin-(20-56)-peptide. Thus the data demonstrate that the Ala19-Glu20 bond in preprotachykinin is the site of cleavage of the signal peptide.

Adrenal Gland Neoplasms↗
PubMed1988

A peptide from the eel pancreas with structural similarity to human pancreatic secretory trypsin inhibitor.

The primary structure of a 61-amino-acid residue peptide from the pancreas of the European eel (Anguilla anguilla) has been established as E E K S G(5)L Y R K P(10)S C G E M(15)S A M H A(20)C P M N F(25)A P V C G(30)T D G N T(35)Y P N E C(40)S L C F Q(45)R Q N T K(50)T D I L I(55)T K D D R(60)C. There was no indication of microheterogeneity. This peptide shows structural similarity to pancreatic secretory trypsin inhibitors from several mammalian species and to a cholecystokinin-releasing peptide isolated from rat pancreatic juice. A comparison of the amino acid sequences of the peptides has identified a domain in the central region of the molecules that has been strongly conserved during evolution. In contrast, the amino acid sequence in the region corresponding to the reactive centre of the mammalian trypsin inhibitors is very poorly conserved in the eel peptide. The P1-P1' reactive site lysine-isoleucine (or arginine-isoleucine) bond in the mammalian trypsin inhibitors is replaced by a methionine-asparagine bond. This region does, however, show limited homology to the reactive centre of human alpha 1-protease inhibitor suggesting that the eel peptide may function as an inhibitor of other proteolytic enzymes in the pancreas.

Amino Acid Sequence↗
PubMed1988

Molecular forms of katacalcin, calcitonin gene-related peptide and gastrin-releasing peptide, in a human medullary thyroid carcinoma.

Peptides synthesized by a human medullary thyroid carcinoma were purified to homogeneity by reverse-phase high performance liquid chromatography and structurally characterized by determination of amino acid composition, amino acid sequence, and fast atom bombardment mass spectra. The katacalcin-related material in the tumor extract was heterogeneous. Katacalcin (1-21) represented the predominant molecular form but metabolites, identified as katacalcin (1-20), (1-19), (1-15) and (1-13), were also identified in high concentration. Calcitonin gene-related peptide-I was isolated from the tumor but calcitonin gene-related peptide-II was absent. A minor component of calcitonin gene-related peptide-like immunoreactivity was of higher molecular weight and may represent an incompletely processed form of the prohormone. Gastrin-releasing peptide (1-27) and gastrin-releasing peptide (18-27) (neuromedin C) were isolated from the tumor but gastrin-releasing peptide (14-27) and bombesin were absent.

Adult↗
PubMed1988

Selective depletion of the acetylcholine and vasoactive intestinal polypeptide of the guinea-pig myenteric plexus by differential mobilization of distinct transmitter pools.

The effect of electrical field stimulation on the release of acetylcholine (ACh) and vasoactive intestinal polypeptide (VIP) from superfused strips of myenteric plexus-longitudinal muscle (MPLM) of guinea-pig ileum and on the transmitter content of the tissue was investigated at different frequencies and in the presence and absence of choline hemicholinium-3 and colchicine. Low frequency electrical field stimulation released ACh by more than 4 times the basal release; the simultaneously detected VIP secretion was increased only slightly above the resting level. During high frequency stimulation (50 Hz) the release of VIP was greatly increased (to 5 times the resting release) whereas the release of ACh increased to only 150% of the basal output. When choline was present, the ACh content of the tissue itself was not altered by electrical stimulation indicating a rate of synthesis sufficient to maintain release. It was reduced in a frequency-dependent manner in the absence of exogenous choline or in the presence of 10 microM hemicholinium-3 (an inhibitor of choline uptake) by up to 54% of the original content. A similar but even larger reduction took place in the amount of ACh released. Neither the secretion of VIP nor the tissue VIP content was altered by these treatments. Long-lasting (greater than 60 min) high-frequency (50 Hz) stimulation resulted in the depletion of the VIP pool (by 25%) while the ACh content remained unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Acetylcholine↗
PubMed1988

Isolation and structural characterization of insulin from the holocephalan fish, Chimaera monstrosa (rabbit fish).

Insulin has been isolated from the pancreas of the holocephalan fish, Chimaera monstrosa (rabbit fish), and characterized by automated Edman degradation and fast atom bombardment mass spectrometry. The primary structure of rabbit fish insulin was identical to that of insulin from the holocephalan fish, Hydrolagus colliei (Pacific ratfish), and contained 21 residues in the A-chain and 38 residues in the B-chain. The amino acid compositions of both rabbit fish and ratfish insulins demonstrated a value consistently lower than that expected for the leucine content of the peptides. It is suggested, therefore, that the insulins were probably isolated as a mixture of the intact peptides and components lacking the C-terminal leucine residue in the B-chain.

Animals↗
PubMed1988

Somatostatin-related and glucagon-related peptides with unusual structural features from the European eel (Anguilla anguilla).

Peptides derived from prosomatostatins I and II and from two distinct proglucagons have been isolated from the pancreas of a teleost fish, the European eel (Anguilla anguilla). The product of prosomatostatin I processing, somatostatin-14, is identical to mammalian somatostatin-14. A 25-amino-acid-residue peptide (Ser-Val-Asp-Asn-Gln5-Gln-Gly-Arg-Glu-Arg10-Lys-Ala-Gly-Cys- Lys15-Asn-Phe-Tyr- Trp-Lys20-Gly-Pro-Thr-Ser-Cys25) is derived from prosomatostatin II. Compared with the corresponding peptides from other teleost fish, the eel somatostatin-25 contains the unusual substitution Pro for Phe at position 22. This peptide was also isolated in a form containing a hydroxylsyl residue at position 20. A 29-amino-acid-residue eel glucagon contains four substitutions relative to human glucagon Asn for Ser8, Glu for Asp15, Thr for Ser16, and Ser for Thr29). In common with mammalian and avian glucagons but unlike most other fish glucagons, the eel peptide possesses a glutamine residue at position 3. A peptide derived from a second proglucagon comprises 36 amino acid residues. A 7-residue C-terminal extension to the glucagon sequence shows structural similarity to the corresponding extension in ratfish (Hydrolagus colliei) glucagon and mammalian oxyntomodulin.

Amino Acid Sequence↗
PubMed1988

Isolation of the tachykinin, des[Ser1Pro2]scyliorhinin II from the intestine of the ray, Torpedo marmorata.

A peptide with neurokinin A-like immunoreactivity was isolated from an extract of the intestine of an elasmobranch fish, Torpedo marmorata. The primary structure of the peptide was established as Ser-Asn-Ser-Lys-Cys-Pro-Asp-Gly-Pro-Asp-Cys-Phe-Val-Gly-Leu-Met.NH2. This amino acid sequence is identical to that of residues (3-18) of scyliorhinin II previously isolated from the intestine of the common dogfish (Scyliorhinus canicula). The presence of the truncated peptide, lacking Ser-Pro, in the Torpedo gut suggests that scyliorhinin II may be a substrate for an enzyme with dipeptidylpeptidase IV-like specificity. The data support previous assertions that strong evolutionary pressure has acted within the elasmobranch subclass of chondrichthyean fish to conserve the structures of regulatory peptides.

Amino Acids↗
PubMed1988

[Arg3]substance P and neurokinin A from chicken small intestine.

Using antisera specific for NH2-terminal and COOH-terminal regions of substance P and for the COOH-terminal region of neurokinin A, peptides with tachykinin-like immunoreactivity were isolated from extracts of chicken small intestine. The peptide Arg-Pro-Arg-Pro-Gln-Gln-Phe-Phe-Gly-Leu-Met-NH2 differs from human substance P by substitution of the lysyl residue by an arginyl residue at position 3. Synthetic [Arg3]substance P showed identical chromatographic and immunochemical properties to chicken substance P and was equipotent with substance P in contracting the guinea pig ileum. A second peptide His-Lys-Thr-Asp-Ser-Phe-Val-Gly-Leu-Met-NH2 isolated from the extracts is identical to human neurokinin A. A third peptide was immunoreactive towards the COOH-terminally directed anti-serum to substance P only but was not characterized structurally in this study.

Amino Acids↗