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R Corder

Publications and source records attributed to R Corder.

At least 91 records · Page 5Linked to original sources

Comparison of the haemodynamic actions of neuropeptide Y, angiotensin II and noradrenaline in anaesthetised cats.

Blood pressure, heart rate, cardiac output, renal flow and femoral flow were recorded in open-chested anaesthetised cats. Dose-response curves were constructed for neuropeptide Y, angiotensin II and noradrenaline after pretreatment with atropine sulphate. Neuropeptide Y, on a molar basis, was 7 and 120 times less potent than noradrenaline and angiotensin, respectively, in producing a 50 mm Hg rise in mean arterial blood pressure. The pressor effect of neuropeptide Y was characterised by dose-dependent increases in total peripheral, renal and femoral resistance with little change in cardiac output. Neuropeptide Y had a similar potency to noradrenaline in causing these resistance changes. However, the pressor response to noradrenaline was associated with a dose-dependent increase in cardiac output. The pressor action of neuropeptide Y was not attenuated by adrenoceptor blockade by phenoxybenzamine (5 mg kg-1) and propranolol (1 mg kg-1).

Anesthesia↗

Chromatographic characterisation of the circulating neuropeptide Y immunoreactivity from patients with phaeochromocytoma.

Samples of adrenal medullary phaeochromocytoma from two patients were extracted in acid. The tissue concentrations of neuropeptide Y (NPY)-like immunoreactivity were found to be 0.94 and 8.11 micrograms/g. Plasma from these patients subjected to NPY radioimmunoassay after Sephadex G-75 gel filtration chromatography revealed circulating plasma concentrations of 1889 and 2079 pg/ml, compared to levels in normal plasma of less than 50 pg/ml, treated in the same way. Further characterisation of this plasma NPY-like immunoreactivity by HPLC showed this peptide to possess identical elution behaviour to human NPY standard. It is suggested that circulating NPY may be a contributory factor in the symptoms exhibited by some patients with adrenal medullary phaeochromocytoma.

Adrenal Gland Neoplasms↗

Pro-opiocortin peptides in rat cerebrospinal fluid.

Cerebrospinal fluid (CSF) taken from rats implanted with chronic cisternal cannulae was subjected to gel filtration chromatography on Sephadex G-50. Fractions were monitored using radioimmunoassays for N-terminal pro-opiocortin (N-POC), gamma 3-melanotropin (gamma 3-MSH), C-terminal adrenocorticotropin (C-ACTH), alpha-endorphin, beta-endorphin, gamma-lipotropin (gamma-LPH) and alpha-MSH. Two peaks which corresponded in elution position to rat N-POC (1-74) and gamma 3-MSH were detected. The major C-ACTH-immunoreactive (IR) peak was found to correspond to 14k ACTH. While no alpha-endorphin immunoreactivity was detected in rat CSF, three beta-endorphin-IR peaks were identified in positions expected for beta-LPH, beta-endorphin (1-31) and beta-endorphin (1-27), as well as a major peak of activity with the elution characteristics and cross-reactivity of rat gamma-LPH. HPLC of the alpha-MSH-IR material in rat CSF revealed the presence of a major peak of immunoreactivity whose retention time did not correspond to the known oxidised and reduced forms of alpha-MSH and its desacetylated and diacetylated derivatives. The identity of this peak is unknown.

Adrenocorticotropic Hormone↗

Purification and characterization of human neuropeptide Y from adrenal-medullary phaeochromocytoma tissue.

Human neuropeptide Y was isolated from acid extracts of adrenal-medullary phaeochromocytoma tissue. After (NH4)2SO4 fractionation, the neuropeptide Y-like immunoreactivity was purified from the resolubilized 80%-saturation-(NH4)2SO4 peptide-rich precipitate, by gel filtration, cation-exchange chromatography and reverse-phase high-pressure liquid chromatography. Amino acid analysis of the peptide revealed a composition almost identical with that of the pig peptide, the exception being the loss of one leucine residue and its replacement with methionine. Tryptic digestion of the peptide and subsequent amino acid analysis of the fragments further confirmed the identity of the peptide. Carboxypeptidase Y digestion of the (1-19)-peptide tryptic fragment has shown the methionine to be located at position 17 in human neuropeptide Y.

Adrenal Gland Neoplasms↗

Demonstration of a neuropeptide Y-like immunoreactivity in human phaeochromocytoma extracts.

Using a porcine neuropeptide Y directed radioimmunoassay it was shown that acid extracts of human phaeochromocytoma tumour tissue contained a neuropeptide Y-like peptide. Further fractionation and purification of this immunoreactivity showed that this human neuropeptide Y-like immunoreactivity was closely similar in molecular size and separation characteristics to porcine neuropeptide Y. The possible contribution of neuropeptide Y to the hypertension characterizing human phaeochromocytoma is discussed.

Chromatography, Gel↗

Regional distribution of pro-opiomelanocortin-derived peptides in the human brain.

The regional distribution of pro-opiocortin-derived peptides and methionine enkephalin was investigated in human brain post-mortem. Sequence-directed radioimmunoassays for beta-endorphin, gamma-lipotropin, adrenocorticotrophin, corticotrophin-like intermediate lobe peptide (ACTH18-39, CLIP) alpha-MSH and methionine enkephalin were used and 40 different human brain areas were assayed. The regional distribution of all the pro-opiomelanocortin-derived immunoreactivities were correlated with highest amounts of beta-endorphin, gamma-lipotropin and ACTH in the hypothalamus, amygdala, periventricular grey, substantia nigra and superior colliculus. The distribution of beta-endorphin, gamma-lipotropin and ACTH did not parallel the distribution of methionine-enkephalin immunoreactivity which was present in the globus pallidus, nucleus accumbens and substantia nigra. Gel exclusion chromatography (G-50) showed that pro-opiocortin-related peptides in the human hypothalamus and periventricular grey separated in positions consistent with the major immunoreactive forms being beta-endorphin, gamma-lipotropin, ACTH and CLIP.

Adrenocorticotropic Hormone↗

Characterization of the somatostatin-like immunoreactivity extracted from an adrenal medullary tumour.

Significant amounts of somatostatin-like immunoreactivity (SLI) were detected in the extract of a human catecholamine-secreting adrenal medullary tumour. After salt fractionation and reconstitution the major portion of SLI was purified by gel filtration and two HPLC steps; in all three systems it eluted in the position of somatostatin-14. The purified somatostatin-like peptide inhibited, in a dose-related manner, growth hormone release from stimulated perfused rat anterior pituitary cells in vitro. Amino acid analysis showed the purified peptide to have an identical composition to somatostatin found in other species.

Adrenal Gland Neoplasms↗

Large-molecular-weight somatostatin in human adrenal medullary tissue.

Three human catecholamine-secreting adrenal medullary tumours, identified as phaeochromocytoma, were found to contain 774, 168, and 78 pmol/g of somatostatin-like immunoreactivity (SLI), compared to 40 pmol/g in a sample of normal human adrenal medulla. Sephadex-G50 gel-filtration chromatography of extracts from these tissues revealed SLI eluting in the position of somatostatin-14, somatostatin-28, and a peak eluting with a mol. wt. of about 5 K. After digestion of eluted material with clostridiopeptidase B, the predominant form of adrenal medullary SLI was found to elute in the position of a 7-K polypeptide.

Adrenal Gland Neoplasms↗

Simultaneous release of neurotensin, somatostatin, enkephalins and catecholamines from perfused cat adrenal glands.

Acid extracts of cat adrenal medullae were found to contain neurotensin-like (0.71 +/- 0.21nmol/gm), met-enkephalin-like (11.71 +/- 2.87nmol/gm), leu-enkephalin-like (1.95 +/- 0.11nmol/gm) and somatostatin-like (1.57 +/- 0.63pmol/gm) immunoreactivities. Using isolated retrogradely perfused cat adrenal glands the secretory responses to acetylcholine (ACh), nicotine and potassium ions (K+) were studied. Spontaneous secretion of catecholamines, neurotensin-like, met-enkephalin-like, leu-enkephalin-like and somatostatin-like immunoreactivities was negligible. However, ACh (5.5 X 10(-5)M), nicotine (2.2 X 10(-5)M) and 55mM K+ all evoked the simultaneous release of noradrenaline, adrenaline and the four neuropeptide immunoreactivities. The ACh stimulated secretion of the four neuropeptides could be prevented by perfusion with hexamethonium (C6, 2.8 X 10(-4)M). The concomitant release of these neuropeptides with catecholamines suggests that they may have a role in the modulation of stress responses.

Acetylcholine↗

Stability of pro-opiocortin-related peptides in post-mortem mouse brain tissue.

The stability of pro-opiocortin-related peptides, growth hormone and somatostatin was investigated in mouse brain for up to 72 h post mortem. The peptide content in acid extracts of whole mouse brain was measured by radioimmunoassay and the molecular forms characterised by chromatography on Sephadex G-50 under acid-dissociating conditions. The brain content of the pro-opiocortin-related peptides and growth hormone rose markedly with time after death and chromatography showed this to be due to an increase in the same molecular forms present immediately post mortem, with no significant peptide fragmentation or precursor cleavage. These rises were not seen in the brains of those animals hypophysectomized at death. In contrast, the levels of somatostatin were not significantly altered post mortem though there was a shift in the relative distribution of immunoactivity between the different molecular forms. These results indicate that the peptide content of post-mortem mouse brain may be affected by leakage of pituitary contents and that even though the levels of other neuropeptides may not change, their molecular forms may be altered.

Adrenocorticotropic Hormone↗

Ectopic production of methionine enkephalin and beta-endorphin.

Immunoreactive methionine enkephalin and beta-endorphin were sought by serial dilution of tissue extracts and assay of chromatographic fractions in non-endocrine tumour tissue from three patients with the ectopic adrenocorticotrophin syndrome associated with carcinoid tumours and in normal lung tissue and thymic tissue from a patient with myasthenia gravis. In all cases serial dilution of extracts showed parellelism to standard radioimmunoassay curves. The two peptides were found in high concentration in the three tumours but were undetectable in the control tissues. In a single case tested the methionine enkephalin concentration in a vein draining the tumour was twice that in a peripheral vein. In view of their profound effect on behaviour in animals and potent analgesic activity in animals and man the ectopic secretion of methionine enkephalin and beta-endorphin may modify the clinical features of a wide variety of tumours and produce some of the diverse clinical syndromes associated with malignancy.

ACTH Syndrome, Ectopic↗

ACTH LPH and related peptides in the ectopic ACTH syndrome.

Adrenocorticotrophin, lipotrophin and the related peptides alpha-MSH, CLIP, beta-endorphin and met-enkephalin have been measured, and characterized chromatographically in tumour extracts from seven patients with the ectopic ACTH syndrome. Four of the seven tumours contained the complete family of peptides, although the proportion of one to another varied between tumours. In addition, large molecule weight forms of ACTH and met-enkephalin were seen. The potential clinical importance of these observations is discussed.

ACTH Syndrome, Ectopic↗

Neuropeptide Y lowers plasma renin activity in the anaesthetised cat.

The effect of intravenously administered neuropeptide Y (NPY) on circulating renin activity has been investigated in the anaesthetized cat. Bolus pressor doses of NPY (100, 300, 1000 and 3000 pmol/kg) produced a dose-related fall in renal conductance and a parallel reduction of plasma renin activity. Low dose infusions of NPY (12.5, 50 and 200 pmol/kg/min) for consecutive 20 min periods had no effect on mean arterial blood pressure or renal conductance, but still produced a concentration dependent fall in plasma renin activity. At the end of the infusion plasma renin activity increased rapidly as the circulating concentration of NPY declined. The infusion study suggests that NPY has a direct inhibitory action on renin secretion.

Animals↗

Pro-enkephalin peptides possessing Met-enkephalin-Arg6-Gly7-Leu8-immunoreactivity in rat CSF, striatum and adrenal gland.

Cerebrospinal fluid (CSF) taken from rats implanted with chronic cisternal cannulae and extracts prepared from rat adrenal gland and striatum were subjected to Sephadex G-50 chromatography and HPLC. Fractions were monitored using specific radioimmunoassays (RIA) for the pentapeptide methionine enkephalin (Met-Enk) and methionine enkephalin-Arg6-Gly7-Leu8 (Met-EnkRGL). In rat CSF, striatum and adrenal gland, three Met-EnkRGL-immunoreactive (IR) peaks of Mrs 8000, 5000 and 1000 daltons were detected. The same peaks were also found to possess Met-Enk-immunoreactivity after enzyme digestion of Sephadex G-50 fractions with trypsin and carboxypeptidase B (CPB), suggesting their derivation from proenkephalin. HPLC of the 8K and 5K peaks on a column of Ultrapore RPSC showed them to elute discretely with similar retention times, indicative of hydrophobic peptides of large molecular weight. Their similar hydrophobicities yet significant separation during gel filtration would suggest that the 8K and 5K peptides are structurally closely related yet different with respect to their molecular weights. HPLC of the small molecular weight material from rat striatum and adrenal gland revealed the presence of Met-EnkRGL and Met-EnkRGL sulphoxide in both tissues. In rat striatum Met-Enk and its sulphoxide were also detected. The oxidised pentapeptide was found to be present in rat CSF, together with two unidentified small molecular weight Met-Enk-IR peaks detected without prior enzyme digestion of fractions. The small molecular weight Met-EnkRGL-IR material in rat CSF was found to be comprised of two unknown peptides which were less hydrophobic than Met-EnkRGL and its sulphoxide derivative.

Adrenal Glands↗

CRF immunoreactive peptides in the human hypophysis: a cautionary note.

By monitoring with a non competitive enzyme linked immunosorbent assay (ELISA), corticotropin releasing factor (CRF)-like immunoreactive material was isolated from the human hypophysis. After acid extraction of peptides from frozen human hypophyses, the purification was achieved by affinity chromatography using purified anti-ovine-CRF IgG bound to a solid phase and then by two HPLC steps using an alkylsilane-bonded large pore size silica. Two CRF-like peptides were purified: discrete immunoreactive peaks coinciding with an optical density peak at 215 nm. Although these peptides were recognized by ELISA, they were not recognized in an RIA using the same anti-ovine-CRF serum and ovine CRF-41 as tracer. Neither of these CRF-immunoreactive peptides had any effect on either the spontaneous or stimulated ACTH release in the perfused isolated anterior pituitary cell bioassay.

Adrenocorticotropic Hormone↗