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J M Conlon

Publications and source records attributed to J M Conlon.

At least 217 records · Page 12Linked to original sources
PubMed1991

Somatostatin, gastrin-releasing peptide and gastrin in the stomach of rats with streptozotocin-induced diabetes and insulinoma.

Somatostatin, gastrin-releasing peptide (GRP) and gastrin were measured in the stomach of rats with streptozotocin-induced diabetes, insulinoma-bearing rats and their respective controls. Rats injected with streptozotocin exhibited hyperphagia, insulinopenia and severe hyperglycemia. Stomach weights, and the concentrations and total amounts of GRP and gastrin in the stomach, were similar to nondiabetic control rats. The concentration of somatostatin in the stomach of diabetic rats was 25% greater, but the total stomach content of somatostatin was similar to that of control rats. Insulinoma-bearing rats exhibited hyperphagia, hyperinsulinemia and hypoglycemia. Concentrations of GRP and gastrin in the stomach were 72% and 19% lower, respectively, than in control rats. Despite 45% greater stomach weight, the total stomach content of GRP was 61% lower. Stomach concentrations of somatostatin, and total stomach contents of somatostatin and gastrin, were similar in insulinoma-bearing and control rats. The results demonstrate abnormalities in the stomach concentrations of regulatory peptides in rats with diabetes and insulinoma. These abnormalities are not attributable to changes in food intake alone, suggesting specific effects of these metabolic diseases on gastric regulatory peptides and gastric function.

Animals↗
PubMed1991

Ranakinin: a novel NK1 tachykinin receptor agonist isolated with neurokinin B from the brain of the frog Rana ridibunda.

An extract of the whole brain of the frog Rana ridibunda contained high concentrations of substance P-like immunoreactivity, measured with an antiserum directed against the COOH-terminal region of mammalian substance P and neurokinin B-like immunoreactivity, measured with an antiserum directed against the NH2-terminus of neurokinin B. The primary structure of the substance P-related peptide (ranakinin) was established as: Lys-Pro-Asn-Pro-Glu-Arg-Phe-Tyr-Gly-Leu-Met-NH2. Mammalian substance P was not present in the extract. The primary structure of the neurokinin B-related peptide was established as: Asp-Met-His-Asp-Phe-Phe-Val-Gly-Leu-Met-NH2. This amino acid sequence is the same as that of mammalian neurokinin B. Ranakinin was equipotent with substance P and [Sar9,Met(O2)11]substance P in inhibiting the binding of 125I-Bolton-Hunter-[Sar9,Met(O2)11]substance P, a selective radioligand for the NK1 receptor, to binding sites in rat submandibular gland membranes (IC50 1.6 +/- 0.3 nM; n = 5). It is concluded that ranakinin is a preferred agonist for the mammalian NK1 tachykinin receptor subtype.

Amino Acid Sequence↗
PubMed1991

Carassin: a tachykinin that is structurally related to neuropeptide-gamma from the brain of the goldfish.

A 21-amino-acid residue tachykinin-related peptide, carassin, was isolated in pure form from an extract of the brain of the goldfish, Carrassius auratus, by reversed-phase HPLC. The primary structure of the peptide was established as the following: Ser-Pro-Ala-Asn-Ala-Gln-Ile-Thr-Arg-Lys-Arg-His-Lys-Ile-Asn- Ser-Phe-Val-Gly-Leu-Met.NH2. This amino acid sequence is the same length as and shows structural similarity (57% homology) to the mammalian tachykinin, neuropeptide-gamma, which is a product of the posttranslational processing of gamma-preprotachykinin. The mammalian tachykinins, substance P and neurokinin B, were not detected in the extract by using specific antisera directed against the NH2-termini of the peptides, but an antiserum directed against the COOH-terminal region of substance P did detect a low concentration of immunoreactive material.

Amino Acids↗
PubMed1991

Structural characterization and biological activity of a neuropeptide Y-related peptide from the dogfish, Scyliorhinus canicula.

A peptide of the pancreatic polypeptide (PP) family was isolated in pure form from the pancreas of an elasmobranch fish, Scyliorhinus canicula (European common dogfish). The primary structure of the peptide was established as: Tyr-Pro-Pro-Lys-Pro-Glu-Asn-Pro-Gly-Glu10-Asp-Ala-Pro- Pro-Glu-Glu-Leu-Ala-Lys-Tyr20-Tyr-Ser-Ala-Leu-Arg-His- Tyr-Ile-Asn-Leu30-Ile-Thr-Arg-Gln-Arg-Tyr.NH2. This sequence contains 86% amino acid sequence homology with human neuropeptide Y, and the COOH-terminal region (residues 20-36) has been fully conserved. Bolus injection of a synthetic replicate of the peptide (0.5-4 nmol) into the celiac artery of conscious dogfish resulted in a significant (P less than 0.01) and dose-dependent increase in arterial blood pressure. A maximum rise in mean pressure (67 +/- 11% over mean basal values; n = 6) was elicited by an injection of 2 nmol peptide. Bolus injections of human neuropeptide Y (0.5-4 nmol) also elicited dose-dependent rises in blood pressure, and the effects produced by the dogfish and human peptides were not significantly different at any dose. The data are consistent with a physiological role for neuropeptide Y-related peptide in cardiovascular regulation in elasmobranch fish.

Amino Acids↗
PubMed1991

Primary structure of frog pituitary adenylate cyclase-activating polypeptide (PACAP) and effects of ovine PACAP on frog pituitary.

Pituitary adenylate cyclase-activating polypeptide (PACAP), a peptide of the glucagon-secretin-vasoactive intestinal polypeptide superfamily, was isolated in pure form from the brain of the European green frog, Rana ridibunda. The primary structure of the peptide indicates that evolutionary pressure to conserve the complete amino acid sequence has been very strong. Frog PACAP comprises 38 amino acid residues and contains only 1 substitution (isoleucine for valine at position 35) compared with human/ovine/rat PACAP. In the presence of the phosphodiesterase inhibitor isobutylmethylxanthine, synthetic ovine PACAP-(1-38) produced a dose-dependent increase in the concentration of cAMP in isolated frog anterior pituitary fragments (ED50 = 2.1 +/- 0.6 x 10(-7) M; mean +/- SE; n = 6). Maximum stimulation (an approximately 8-fold increase in concentration over basal values) was produced by 10(-6) M peptide. The truncated form of PACAP [PACAP-(1-27)] also produced a dose-dependent increase in cAMP in frog anterior pituitary fragments, and the potency of the peptide (ED50 = 5.9 +/- 0.6 x 10(-8) M) was comparable to that of PACAP-(1-38). The data suggest, therefore, that the function as well as the structure of PACAP have been conserved during the evolution of amphibia to mammals.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Post-translational processing of prepro-urotensin II.

The primary structure of a teleost prepro-urotensin II may be deduced from the nucleotide sequence of cloned DNA complementary to carp prepro-urotensin II mRNA but the pathway of post-translational processing of the precursor is unknown. In this study, we have isolated four peptides from an extract of flounder urophysis that are derived from prepro-urotensin II by proteolytic cleavage. The amino acid sequences of the peptides demonstrate that flounder prepro-urotensin II is cleaved at two monobasic processing sites (single arginine residues) to generate peptides with limited homology to carp prepro-urotensin II-(22-41)-, -(42-87)- and -(88-110)-peptides. Cleavage at a tribasic residue processing site generates a urotensin II with the primary structure: Ala-Gly-Thr-Thr-Glu-Cys-Phe-Trp-Lys-Tyr-Cys-Val. Urotensin II-(4-12)-peptide represented a minor component in the extract.

Amino Acid Sequence↗
PubMed1990

[Ser5]-somatostatin-14: isolation from the pancreas of a holocephalan fish, the Pacific ratfish (Hydrolagus colliei).

The holocephalan fishes were the first class of vertebrate in evolution to develop a pancreatic gland with both endocrine and exocrine parenchyma. An extract of the pancreas of one such fish, the Pacific ratfish (Hydrolagus colliei) contained somatostatin-like immunoreactivity (141 pmol/g wet wt), measured with an antiserum raised against mammalian somatostatin-14. Automated Edman degradation and fast atom bombardment-mass spectrometry established the primary structure of the major molecular form as Ala-Gly-Cys-Lys-Ser-Phe-Phe-Trp-Lys-Thr-Phe-Thr-Ser-Cys. A minor component of somatostatin-like immunoreactivity, constituting 8% of the total, was of approximate molecular weight 6000. Thus, in the ratfish pancreas prosomatostatin-I is processed predominantly to somatostatin-14, as in the mammalian pancreas, but the resulting tetradecapeptide contains the substitution Ser for Asn at position 5.

Amino Acid Sequence↗
PubMed1990

Isolation and biological activity of a novel kinin ([Thr6] bradykinin) from the turtle, Pseudemys scripta.

Incubation of plasma from the red-eared turtle with glass beads in the presence of the kininase inhibitor 1,10-phenanthroline resulted in activation of the kallikrein-kinin system and generation of bradykinin-like immunoreactivity. The immunoreactive material comprised a single molecular form that was purified to homogeneity by reverse phase HPLC. The primary structure of the peptide was determined by automated Edman degradation and fast atom bombardment mass spectrometry. The amino acid sequence of the turtle kinin Arg-Pro-Pro-Gly-Phe-Thr-Pro-Phe-Arg contains the substitution Thr for Ser at position 6 compared with mammalian bradykinin. [Thr6] bradykinin was synthesized using solid phase methodology, and bolus injections of the peptide into the left atrium of the anaesthetized turtle produced rapid vasodilation. A dose-dependent increase in blood flow in the left aortic arch was accompanied by a decrease in peripheral vascular resistance, so that systemic blood pressure did not change. The data suggest that the kallikrein-kinin system may play an important physiological role in the regulation of cardiovascular function in reptiles.

Amino Acid Sequence↗
PubMed1990

Glucagon-like peptide-1(7-36)amide: characterization of the domain responsible for binding to its receptor on rat insulinoma RINm5F cells.

Glucagon-like peptide-1(7-36)amide (GLP-1(7-36)amide) is a potent stimulator of insulin secretion. Receptors for this hormone have been found on different insulinoma-derived cell lines, e.g. the RINm5F cell line which is derived from a radiation-induced rat insulinoma. To characterize the part of the GLP-1(7-36)amide molecule that is responsible for binding to its receptor on RINm5F cells, binding studies with synthetic C-terminal (GLP-1(21-36)amide) and synthetic N-terminal (GLP-1(7-25] GLP-1 fragments were carried out. GLP-1(21-36)amide showed dose-dependent binding to the GLP-1(7-36)amide receptor but was approximately 1500 times less potent in inhibiting binding of 125I-labelled GLP-1(7-36)amide than the intact hormone. GLP-1(7-25) at concentrations up to 10 mumol/l did not inhibit binding of label. Neither fragment changed intracellular cyclic AMP concentrations, in contrast to GLP-1(7-36)amide which increased intracellular cyclic AMP. GLP-1(21-36)amide, however, acted as a weak partial antagonist of GLP-1(7-36)amide with respect to GLP-1(7-36)amide-dependent stimulation of cyclic AMP production.

Animals↗
PubMed1990

Effects of gastric inhibitory polypeptide, vasoactive intestinal polypeptide and peptide histidine isoleucine on the secretion of hormones by isolated mouse pancreatic islets.

The release of insulin, glucagon, somatostatin and pancreatic polypeptide (PP) by isolated mouse pancreatic islets was determined during 30-min incubations at 5.6 and 16.7 mmol glucose/l in the absence and presence of gastric inhibitory polypeptide (GIP), vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) at concentrations of 1-1000 nmol/l. Insulin release was enhanced (greater than 50%) by GIP (100-1000 nmol/l) and VIP (1 mumol/l) at 5.6 mmol glucose/l, but not at 16.7 mmol glucose/l. Glucagon release was increased by GIP (100-1000 nmol/l), and by VIP and PHI (1-1000 nmol/l) at both glucose concentrations in a dose-related manner (maximum increases greater than tenfold). Somatostatin release was similarly increased by GIP (10-1000 nmol/l) at both glucose concentrations. Only the highest concentration (1 mumol/l) of PHI tested increased somatostatin release (twofold) at 5.6 mmol glucose/l, whereas PHI and VIP (1-1000 nmol/l) reduced (greater than 37%) somatostatin release at 16.7 mmol glucose/l. PP release was increased (49-58%) by 100-1000 nmol GIP/l, but was not significantly altered by VIP, and was reduced (39-56%) by PHI. The results indicate that GIP, VIP and PHI each stimulate glucagon release in a dose-related manner, but they exert discretely different effects on other islet hormones depending upon the dose and the prevailing glucose concentration.

Animals↗
PubMed1990

Effect of gastrin-releasing peptide on the secretion of mouse islet hormones in vitro.

Collagenase-isolated mouse islets were incubated with gastrin-releasing peptide (GRP). At 5.6 mmol glucose/l. 10 nmol GRP/l increased the release of insulin (by 50%) and glucagon (by twofold), decreased the release of pancreatic polypeptide (by 35%), but did not significantly affect the release of somatostatin. At 16.7 mmol glucose/l, 10 nmol GRP/l increased glucagon release (by fivefold) and decreased pancreatic polypeptide release (by 46%), without significantly altering insulin and somatostatin release. GRP (200 nmol/l) did not affect insulin release by perifused mouse islets at 2.8 mmol glucose/l, but increased both first and second phase insulin release after a square wave increase in the glucose concentration to 11.1 mmol/l. At 5.6 mmol glucose/l, GRP (100 pmol/1-100 nmol/l) increased (by 50-70%) insulin release by the RINm5F clonal cell line. GRP did not affect glucose oxidation or the cyclic adenosine monophosphate content of RINm5F cells. However, the intracellular free Ca2+ concentration of RINm5F cells was rapidly and transiently increased by GRP (maximum increase of 64% about 10 s after exposure to 1 mumol GRP/l). The rise of intracellular free Ca2+ was approximately halved in the absence of extracellular Ca2+. The results suggest that GRP may contribute to the normal regulation of the endocrine pancreas. The insulin-releasing effect of GRP is mediated via increased cytosolic free Ca2+, derived both from an increased net influx of extracellular Ca2+ and from mobilization of intracellular Ca2+ stores.

Animals↗
PubMed1989

Evidence that neuromedin U may regulate gut motility in reptiles but not in mammals.

Neuromedin U-8 induced a monophasic and concentration-dependent contraction of intact small intestine from the turtle, Pseudemys scripta, whereas the peptide had no effect upon the motility of rat and guinea pig gut. The maximum response produced by neuromedin U-8 was 56% of that produced by acetylcholine and 62% of that produced by potassium chloride. The potency and maximum response to neuromedin U-8 were unaffected by tetrodotoxin and atropine. The data suggest that neuromedin U may play a role in regulation of gut motility in lower vertebrates but not in mammals.

Acetylcholine↗
PubMed1989

Calcitonin gene-related peptides relax guinea pig and rat gastric smooth muscle.

Rat and human alpha- and beta-calcitonin gene-related peptide (CGRP), in the concentration range 1-100 nM, produced sustained relaxations of longitudinal muscle from the rat fundus and guinea pig gastric corpus. The peptides were equipotent and equally effective. Tetrodotoxin, adrenoceptor and purine receptor antagonists, somatostatin, apamin and Tyr-rat alpha-CGRP-(28-37) peptide did not modify the action of the CGRP peptides. The CGRP-induced responses were inhibited by verapamil and potentiated by Bay K-8644. Incubation of the tissues with indomethacin markedly reduced the magnitude of the CGRP- and adrenaline-induced relaxations, but their responsiveness was restored by addition of prostaglandins E1, E2 and F2 alpha in concentrations that alone did not affect the motility of the indomethacin-treated strips. It is suggested that an inhibitory receptor for CGRP on gastric smooth muscle cells is linked to calcium channels and may be activated or sensitized by endogenous prostaglandins.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1989

Effect of a long-acting somatostatin analogue (octreotide) on circulating tachykinins and the pentagastrin-induced carcinoid flush.

Cutaneous flushing was provoked in seven patients with metastatic carcinoid tumours and the carcinoid syndrome by an intravenous injection of pentagastrin (0.6 micrograms.kg-1 body weight). The patients were studied before and 1 h after a subcutaneous injection of the long-acting somatostatin analogue octreotide 50 micrograms (Sandostatin). The severity of the carcinoid flush in all the patients was reduced by administration of the analogue. The rise in facial temperature was 1.3 (0.3) degree C before and 0.8 (0.2) degree C after octreotide. Six patients responded to pentagastrin with a rise in the circulating neurokinin A-like immunoreactivity (NKA-LI) and five patients with a rise in circulating substance P-like immunoreactivity (SP-LI). No cutaneous flushing or rise in tachykinin concentration was observed in healthy subjects (n = 6) after injection of pentagastrin. The rise in NKA-LI in the patients was decreased by 61 (14)% and the rise in SP-LI by 54 (13)% after octreotide. Although flushing still occurred, the tachykinin response in two patients was completely abolished. The data demonstrate that the release of tachykinins from carcinoid tumours during pentagastrin-induced flushing is subject to partial inhibition by octreotide. However, the occurrence of a flush in some patients in the absence of a detectable rise in circulating tachykinins indicates that the latter peptides cannot be the sole causative agent of the carcinoid flush.

Aged↗
PubMed1989

Multiple molecular forms of insulin and glucagon-like peptide from the Pacific ratfish (Hydrolagus colliei).

The primary structure of an insulin isolated from the pancreas of the holocephalan fish, Hydrolagus colliei (Pacific ratfish), has been established as A-chain: GIVEQCCHNTCSLANLEGYCN B-chain: VPTQRLCGSHLVDALYFVCGERGFFYSPKPIRELEPLL. Three further molecular forms of insulin were also isolated and shown to have the same A-chain but truncated B-chains of 31-, 36-, and 37-amino acid residues. It is proposed that all four insulins arise from a single proinsulin by proteolytic cleavages at different sites within the C-peptide region. The insulin with 38 amino acids in the B-chain was equipotent with human insulin in inhibiting the binding of radiolabelled human insulin to rat fat cells but the maximum effect of ratfish insulin upon the transport of 3-O-methylglucose into the cells was only 65% of the maximum effect of human insulin. Two molecular forms of glucagon-like peptide were isolated from the ratfish pancreas. The primary structure of the more abundant peptide was established as HADGIYTSDVASLTDYLKSKRFVESLSNYNRKQND. The primary structure of the second peptide was the same except that it was extended from the C-terminus by the sequence RRM. It is probable, therefore, that both glucagon-like peptides also arise from a single proglucagon by different pathways of post-translational processing.

Amino Acid Sequence↗
PubMed1989

Neurohormonal peptides in the gut of the Atlantic hagfish (Myxine glutinosa) detected using antisera raised against mammalian regulatory peptides.

Concentrations of regulatory peptides in an extract of the intestine of the cyclostome, Myxine glutinosa (Atlantic hagfish), were measured by radioimmunoassay using 12 antisera of defined regional specificity that were raised against mammalian gastrointestinal peptides. The hagfish gut contained somatostatin-, cholecystokinin/gastrin-, C-terminal substance P-, and neurokinin A-like immunoreactivity in concentrations that were 10 to 100 times less than the corresponding concentrations in the rat intestine. The hagfish gut also contained glucagon-like immunoreactivity, measured with both C- and N-terminally directed antisera, but the immunoreactivity did not dilute in parallel with the porcine glucagon standard in radio-immunoassay. No immunoreactivity was detected using antisera to calcitonin gene-related peptide, gastrin-releasing peptide, neuromedin U, neurotensin, N-terminal substance P, and vasoactive intestinal polypeptide. The somatostatin-like immunoreactivity in the hagfish gut was resolved by HPLC into components with the retention times of somatostatin-34 and somatostatin-14, previously isolated from the hagfish islet organ (relative abundance 2:1). The retention times of hagfish glucagon and of the multiple molecular forms of the tachykinin-like peptides were appreciably different from the retention times of the corresponding mammalian peptides.

Animals↗
PubMed1989

CCK-antagonist L-364,718: influence on rat pancreatic growth induced by caerulein and bombesin-like peptides.

The present study investigates the inhibitory effect of the novel potent benzodiazepine-related CCK-antagonist L-364,718 on pancreatic growth in the rat induced by chronic administration of caerulein and bombesin-like peptides. Caerulein, injected s.c. twice daily at a dose of 1 microgram/kg body weight, and bombesin (10 micrograms/kg) induced a similar increase (1.5-3-fold) in pancreatic wet weight, total protein, amylase, trypsin, putrescine and spermidine content after 14 days of treatment. Growth induced by caerulein showed a significant increase in total DNA content suggesting cellular hyperplasia, whereas bombesin-like peptides led to cellular hypertrophy. In comparison to bombesin the decapeptide neuromedin C (10 micrograms/kg) was found to be 30-50% less potent. In the same dose range, neuromedin B and the tachykinins neurokinin A and B, all structurally related to bombesin, had no significant trophic effect on the rat pancreas. Administration of the CCK-antagonist L-364,718 twice daily at a dose of 0.1 mg/kg or at 1.0 mg/kg, either s.c. or orally, led dose-dependently to a near-complete inhibition of the caerulein-induced trophic effect. In contrast, L-364,718 administered at identical dosages, did not affect pancreatic hypertrophy induced by bombesin and neuromedin C. It is concluded that both peptides mediate their effect on the rat pancreas directly and not via release of endogenous cholecystokinin. Tachykinins are not involved in the regulation of pancreatic growth. Caerulein- and bombesin-like peptides have comparable effects on the stimulation of protein and polyamine synthesis.

Amino Acid Sequence↗