Biomedical subjects

R Corder

Publications and source records attributed to R Corder.

At least 73 records · Page 4Linked to original sources

PubMed1990

Regional distribution of neuropeptide Y-like immunoreactivity in human hypothalamus measured by immunoradiometric assay: possible influence of chronic respiratory failure on tissue levels.

The regional distribution of neuropeptide Y-like immunoreactivity (NPY-IR) in the human hypothalamus has been determined using a highly specific immunoradiometric assay. Hypothalami were removed during postmortem examination from 19 subjects. The pituitary stalk and 11 anatomically defined nuclei and areas were microdissected from one or both sides of each hypothalamus. NPY-IR was detectable in the acid extracts of tissue samples prepared from all the hypothalamic regions studied, with the highest concentrations being found in the infundibular nucleus (325 +/- 53 fmol/mg wet weight of tissue) and the ventromedial nucleus (217 +/- 22 fmol/mg). For the 11 subjects where both sides of the hypothalamus were dissected, values obtained for the areas in one half showed a good degree of symmetry with the corresponding areas on the contralateral side. The infundibular nucleus exhibited the greatest range of values (72-1,137 fmol/mg). Interestingly, variations in other parts of the hypothalamus were observed to parallel those of this nucleus. Expressed as correlation coefficients (r), levels in the infundibular nucleus appeared to be most closely related to those of the ventromedial nucleus (VM; r = 0.89) and paraventricular nucleus (PV; r = 0.84). In addition, retrospective analysis of the clinical histories showed that all patients with very high NPY levels in the infundibular nucleus (621.0 +/- 107.7 fmol/mg; n = 8) had suffered from respiratory failure or severe dyspnea of at least 10 days duration prior to death. The remaining patients (166.7 +/- 17.1 fmol/mg; n = 11) had either died 48 h from the onset of cardiorespiratory difficulties or of unrelated causes.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1990

Depletion of hypothalamic growth hormone-releasing hormone by neonatal monosodium glutamate treatment reveals an inhibitory effect of betamethasone on growth hormone secretion in adult rats.

Rats were treated with monosodium glutamate (MSG), 4 mg/g on alternate days for the first 10 days of life, to induce lesions of the arcuate nucleus and destroy the majority of growth hormone-releasing hormone (GHRH) neurones. At 10 weeks of age, control (n = 42) and MSG-treated (n = 36) male rats were used to test the effect of glucocorticoids on growth hormone (GH) secretion. Each treatment group was divided into six study groups to determine the effect of betamethasone (BM), administered either 3 or 20 h prior to sacrifice, alone and in combination with hypoglycaemia (insulin 0.1 U/100 g). BM treatment of male rats was without effect on plasma GH levels in control animals. In contrast, glucocorticoid administered either 3 h before sacrifice or the previous evening significantly reduced circulating GH (p less than 0.001) in MSG-treated animals. The difference in plasma GH response to BM pretreatment in control rats and those with lesions of the arcuate nucleus indicates a hypothalamic action of glucocorticoids, presumably on somatostatin and GHRH neurones. In control animals the effects appear to be counterbalancing, but following destruction of GHRH neurones an uncompensated inhibitory influence was observed. Male MSG-treated rats had lower body weight (-25%) and reduced hypothalamic GHRH (-89%) and pituitary GH content (-69%) compared to male controls. Female rats which had undergone the same neonatal MSG treatment (n = 40) when sacrificed 1 week after their male counterparts showed similar reductions in body weight (-15%), hypothalamic GHRH (-74%), and pituitary GH (-67%).(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1990

Stimulation of growth hormone release in man by the potent D2-dopamine agonist CV 205-502: comparison of responses to intravenous and oral administration.

It is well known that dopaminergic agents are stimulators of GH release in man, and although responses are sometimes unreliable, oral L-dopa and iv dopamine have frequently been employed in the evaluation of GH-deficient states. To assess the effects on GH secretion of a new potent D2-dopamine agonist, the octahydrobenzo(g)quinoline CV 205-502 (CV) we have investigated the GH responses in healthy male volunteers to four different iv doses. For this purpose 3 separate groups of 9 subjects were studied. The respective groups were administered on separate occasions 10 micrograms CV and placebo (group 1), 5 micrograms, 2.5 micrograms, and placebo (group 2), and 1 microgram and placebo (group 3). Each subject received drug and placebo in a double blind randomly assigned order, with at least 5 days between their administration. Active compound or placebo was infused over 30 min, and blood sampling was carried out for 72 h after cessation of infusion. Peak GH levels occurred between 45-60 min after the end of the infusion; the observed maximum GH concentrations were 19.2 +/- 2.9 micrograms/L (10 micrograms, iv; P less than 0.001 vs. placebo), 9.61 +/- 2.1 (5 micrograms, iv; P less than 0.001 vs. placebo), 4.7 +/- 1.7 (2.5 micrograms, iv; P less than 0.05 vs. placebo), and 1.9 +/- 0.8 micrograms/L (1 micrograms, iv; P = NS vs. placebo). The mean integrated GH secretion expressed in arbitrary units [area under the response curve (AUC)] up to 3 h postinfusion showed a typical dose-response relationship. Mean values were 1715 +/- 269.4 (10 micrograms, iv; P less than 0.001 vs. placebo), 956.1 +/- 189.9 (5 micrograms, iv; P less than 0.001 vs. placebo), 312.8 +/- 105.8 (2.5 micrograms, iv), and 162.8 +/- 47.5 (1 microgram, iv). In a second study with a separate group of 18 volunteers, we compared the GH response to an oral dose of 100 micrograms CV with those to 5 micrograms CV given iv and placebo treatment. Peak GH values in this study were 20.3 +/- 5.5 micrograms/L (100 micrograms, orally; P less than 0.01 vs. placebo) and 14.6 +/- 2.8 (5 micrograms, iv; P less than 0.001 vs. placebo). Maximum levels occurred 45 min after the infusion and 90 min after ingestion (60 min relative to the end of the infusion).(ABSTRACT TRUNCATED AT 400 WORDS)

Administration, Oral↗

PubMed1989

A physiological role for neuropeptide Y in regulating the estrogen/progesterone induced luteinizing hormone surge in ovariectomized rats.

To test the hypothesis that neuropeptide Y (NPY) is involved in the regulation of the estrogen/progesterone-induced luteinizing hormone (LH) surge in ovariectomized rats, we passively immunized animals against NPY by administering purified immunoglobulins raised against the peptide directly into the central nervous system. Ovariectomized rats were prepared with an intracerebroventricular (i.c.v.) guide cannula and an intravenous catheter prior to experimentation. On day 1 of the experiment the animals received a 5-microliters i.c.v. injection of a highly specific immunoglobulin against NPY (NPY-ab) and a 50-micrograms injection of estradiol benzoate. The antibody injection was repeated on days 2 and 3 of the experiment. On day 3, animals received a 2.5-mg injection of progesterone. Control animals were treated in exactly the same fashion except that a nonspecific control immunoglobulin was injected i.c.v. rather than the NPY-ab. As expected, the steroid-primed animals treated with the control antibodies exhibited large surges in LH secretion approximately 4 h following the progesterone injection. Concentrations rose from 4.2 +/- 1.0 to 27.9 +/- 9.9 ng/ml. In marked contrast, the NPY-ab-treated animals demonstrated no increase in LH concentrations. Baseline values were 3.1 +/- 0.3 ng/ml and remained unchanged (maximum concentrations were 3.8 +/- 1.9 ng/ml) following the progesterone injection. These results demonstrate that hypothalamic NPY plays a role in mediating the estradiol/progesterone-induced gonadotropin surge and suggests that this neuropeptide plays a physiological role in normal ovulatory surges of LH and FSH.

Animals↗

PubMed1989

Study of the influence of stress and adrenalectomy on central and peripheral neuropeptide Y levels. Comparison with catecholamines.

Neuropeptide Y (NPY) is colocalized with catecholamines in brainstem-hypothalamus neuronal pathways implicated in the regulation of the hypothalamo-hypophyso-adrenocortical system (HHAS) and may interact with catecholamines in the regulation of neuroendocrine stress responses. On the other hand, the presence of corticosteroid receptors in these neurons suggests that adrenocortical hormones may regulate central NPY levels. NPY and biogenic amine levels were therefore measured in punched brain regions (ventrolateral and dorsomedial medulla, paraventricular and arcuate nucleus of the hypothalamus, frontal cortex) in basal conditions and up to 4 h after a 30-min period of restraint stress. Despite a massive activation of the HHAS (measured by plasma levels of ACTH and glucocorticoids), and a large increase of prolactin levels, no change of NPY levels could be found in any of the above-mentioned structures. The same parameters, as well as plasma levels of NPY and catecholamines and NPY levels in cardiac tissue were also measured 2, 20 and 96 h after adrenalectomy. Again, despite the large changes of brain and peripheral catecholamine levels, and the intense activation of the HHAS, no change of NPY levels was observed in any of the structures studied. These data question the nature of the relationships between NPY and neuroendocrine stress responses.

Adrenal Glands↗

PubMed1988

Isolation and sequence of rat peptide YY and neuropeptide Y.

Rat peptide YY and rat neuropeptide Y have been isolated in parallel from colon and brain extracts respectively, using salt fractionation, gel filtration chromatography, cation-exchange HPLC, and reverse phase phenyl-silica HPLC. Immunoreactivity was identified using a combination of 3 NPY immunoassays which exhibit differing cross-reactivities for PYY (90%, less than 0.01% and 30% respectively). The yield at the final purification step was 1.2 nmol rPYY and 0.5 nmol rNPY. Half of each purified peptide was subjected to complete microsequence analysis. This showed that while rat NPY was structurally identical to human NPY, the sequence of PYY from rat colon was the same as porcine PYY isolated from extracts of duodenum.

Amino Acid Sequence↗

PubMed1988

Dexamethasone treatment increases neuropeptide Y levels in rat hypothalamic neurones.

Immunoreactive glucocorticoid receptors (GR) have previously been demonstrated in neuropeptide Y (NPY) neurones of the rat hypothalamus. To determine whether NPY synthesis is influenced by glucocorticoids, the effect of dexamethasone (DEX) on the levels of immunoreactive NPY in rat hypothalamic neurones was investigated in vivo and in vitro. Daily injections of DEX (0.1 mg/day) for 5 days increased the NPY content of the mediobasal hypothalamus in female rats by 117% (p less than 0.002). Primary cultures of hypothalamic neurones were also sensitive to the effect of glucocorticoids. Intracellular NPY levels were significantly increased (p less than 0.001) compared to control values by 151%, 222% and 268% when cultures were maintained in a defined serum free medium containing DEX 10(-9), 10(-8) and 10(-7) M respectively.

Animals↗

PubMed1988

Cardiovascular effects of neuropeptide Y.

Neuropeptide Y (NPY) is present in the brain, the adrenal medulla, and peripheral sympathetic nerves. This peptide is released together with catecholamines during sympathoadrenal activation. It possesses direct vasoconstrictor properties that are not dependent on simultaneous adrenergic activation. Moreover, it potentiates the vascular effect of several stimulatory substances and may contribute to the modulation of blood pressure responsiveness under a number of circumstances. NPY may also be indirectly involved in the control of blood pressure through regulating the release of hormones with well-established actions on the cardiovascular system.

Adrenal Medulla↗

PubMed1988

Effect of ganglion blockade with pentolinium on circulating neuropeptide Y levels in conscious rats.

The vasoconstrictor peptide, neuropeptide Y (NPY), is present in perivascular noradrenergic neurons of all mammals studied and may be important in the regulation of blood pressure. High plasma levels of NPY have been measured in the rat. To investigate partially the source and factors controlling the release of the circulating peptide, the effect of pentolinium tartrate administration has been studied in conscious rats. Pentolinium given as a bolus (5 mg/kg) followed by an infusion of a further 5 mg/kg/30 min produced a highly significant reduction in blood pressure of more than 40 mm Hg, when compared to either basal values or control animals treated with saline. Pentolinium treatment resulted in significantly lower plasma neuropeptide Y levels (31.0 +/- 6.7 fmol/ml) compared with those of control animals (78.6 +/- 8.2 fmol/ml). Circulating catecholamines were also significantly reduced in those animals receiving pentolinium. These results are compatible with circulating NPY arising from the sympathetic nervous system, with release being controlled by the mechanisms already established for catecholamines.

Animals↗

PubMed1988

The actions of neuropeptide Y and peptide YY on the hepatic arterial and portal vascular beds of the anaesthetized dog.

1. The vascular actions of the two peptides, neuropeptide Y (NPY) and peptide YY (PYY) were compared with the transmitter noradrenaline (NA) on the arterial and portal vascular beds of the in situ liver of the anaesthetized dog. 2. The sole vascular response of the hepatic arterial vasculature to intra-arterial administration of either NPY or PYY was vasoconstriction; the duration of these responses was longer than that to NA. 3. The maximum hepatic arterial vasoconstrictor responses to PYY and to NPY were significantly different and they were both significantly less than the maximum to NA (P less than 0.001). 4. In contrast to its activity on the splenic arterial vasculature PYY was not more potent, on a molar basis, than NPY as an hepatic arterial vasoconstrictor agent. However, both peptides were significantly more potent than NA (P less than 0.005). 5. Neither peptide, when injected intraportally, caused any change in intrahepatic portal inflow resistance. 6. Both peptides when administered intraportally in doses which were free of systemic effects caused hepatic arterial vasoconstriction.

Anesthesia↗

PubMed1988

A comparison of the differential effects of vasoactive intestinal peptide and peptide histidine isoleucine on the vascular and capsular smooth muscle of the dog spleen.

1. The actions of the two peptides, vasoactive intestinal peptide (VIP) and peptide histidine isoleucine (PHI) have been compared to that of isoprenaline on the smooth muscle systems of the isolated blood-perfused dog spleen. 2. Intra-arterial injections of VIP and PHI caused graded increases in splenic arterial blood flow at constant perfusion pressure indicative of splenic arterial vasodilatation. 3. VIP was significantly more potent than PHI, with their respective molar ED50 values being 9.9 +/- 3.7 and 830 +/- 141 pmol (P less than 0.002). VIP was approximately 10 and 200 times more potent than isoprenaline and PHI respectively. 4. The maximum reduction in splenic arterial vascular resistance was the same (P greater than 0.5) in response to intra-arterial VIP and PHI, although both peptide maxima were significantly less (P less than 0.05, 0.01 respectively) than that obtained with isoprenaline. 5. Small increases in spleen volume accompanied the splenic vasodilator responses to both peptides. They were probably passive in origin, secondary to splenic arterial vasodilatation. 6. The selective beta 2-adrenoceptor antagonist, ICI 118,551, did not antagonize the splenic arterial vasodilator response to VIP or PHI but markedly attenuated the effect of isoprenaline. 7. These observations indicate that VIP and PHI, when either co-released locally or present together in the systemic circulation, may exert a differential action on different components of the circulation.

Adrenergic beta-Antagonists↗

PubMed1988

Plasma levels of neuropeptide tyrosine Y (NPY) are increased in human sepsis but are unchanged during canine endotoxin shock despite raised catecholamine concentrations.

Alterations in levels of adrenal vein and circulating immunoreactive neuropeptide tyrosine Y (NPY), as well as systemic catecholamine concentrations, have been investigated in the dog after endotoxin administration. Eighteen dogs were anaesthetized with alpha-chloralose and allowed to breathe spontaneously. Severe shock was produced by the administration of a large bolus of Escherichia coli endotoxin followed by a continuous infusion. In two further animals the left lumbar adrenal vein was cannulated and an intermittent choke allowed retrograde sampling of the adrenal effluent. The production of hypodynamic shock was associated with marked increases in systemic catecholamine concentrations but there were no consistent changes in adrenal vein or systemic immunoreactive NPY levels. In contrast, circulating concentrations of immunoreactive NPY were markedly raised above the normal range in five patients with septic shock.

Animals↗

PubMed1987

Markedly reduced blood pressure responsiveness in endotoxemic rats; reversal by neuropeptide Y.

This study in conscious normotensive rats was performed to assess the effect of the vasoconstrictor peptide, neuropeptide Y (NPY), on blood pressure responsiveness to exogenous norepinephrine in endotoxaemia. NPY and endotoxin were infused at doses which had no effect on blood pressure, whether given alone or in combination. Endotoxin markedly reduced the pressor responses to bolus injections of norepinephrine. However, blood pressure responsiveness could be enhanced by infusing NPY simultaneously with the endotoxin. It is suggested that low dose NPY infusions may be clinically useful in reversing the reduced vascular responsiveness to pressor amines in shock.

Adrenal Medulla↗

PubMed1987

Identification of human synenkephalin-like immunoreactivity in phaeochromocytoma tissue using a novel carboxy-terminal radioimmunoassay.

An antiserum raised against the synthetic tyrosinylated carboxy-terminal sequence of synenkephalin (Tyr-Glu-Glu-Ser-His-Leu-Leu-Ala) has been used to chromatographically characterize the human synenkephalin-like immunoreactivity extracted from 3 adrenal medullary phaeochromocytomas. Gel filtration chromatography identified in each tumor a single peak of 8 kDa which on subsequent ion-exchange chromatography had the elution characteristics of an acidic polypeptide. These results are compatible with the human synenkephalin sequence predicted from cDNA studies, and indicate that this is the authentic peptide.

Adrenal Gland Neoplasms↗

PubMed1987

Influence of sodium intake on circulating levels of neuropeptide Y.

Neuropeptide Y (NPY) is present in the adrenal medulla, in sympathetic neurons as well as in the circulation. This peptide not only exerts a direct vasoconstrictor effect, but also potentiates the vasoconstriction evoked by norepinephrine and sympathetic nerve stimulation. The vasoconstrictor effect of norepinephrine is also enhanced by salt loading and reduced by salt depletion. The purpose of this study was therefore to assess whether there exists a relationship between dietary sodium intake and the levels of circulating NPY. Uninephrectomized normotensive rats were maintained for 3 weeks either on a low, a regular or a high sodium intake. On the day of the experiment, plasma levels of NPY and catecholamines were measured in the unanesthetized animals. There was no significant difference in plasma norepinephrine and epinephrine levels between the 3 groups of rats. Plasma NPY levels were the lowest (65.4 +/- 8.8 fmol/ml, n-10, Mean +/- SEM) in salt-restricted and the highest (151.2 +/- 25 fmol/ml, n-14, p less than 0.02) in salt-loaded animals. Intermediate values were obtained in rats kept on a regular sodium intake (117.6 +/- 20.1 fmol/ml). These findings are therefore compatible with the hypothesis that sodium balance might to some extent influence blood pressure regulation via changes in circulating NPY levels which in turn modify blood pressure responsiveness.

Animals↗

PubMed1987

Stress-induced changes of circulating neuropeptide Y in the rat: comparison with catecholamines.

Circulating concentrations of neuropeptide Y-like immunoreactivity (NPY), noradrenaline (NA) and adrenaline (AD) were measured in conscious, chronically catheterized rats submitted to various stress protocols. Basal plasma levels of NPY, NA and AD (194 +/- 52 fmol/ml, 0.90 +/- 0.11 pmol/ml and 0.52 +/- 0.07 pmol/ml) were increased by handling (+132%, +76% and +629%, respectively) and rose further during electric shock treatment. Adrenalectomy resulted in the complete disappearance of circulating adrenaline but did not alter either control or stress values of noradrenaline. In comparison circulating levels of NPY were reduced, but not significantly in adrenalectomized animals. Insulin stress induced a large increase in plasma AD levels and cold stress induced an increase in plasma NA levels, without any parallel change in NPY concentrations. These results demonstrate that NPY, which is colocalized with catecholamines in the peripheral nervous systems, is also released during stress responses and that its release parallels more closely changes in circulating NA than AD. Furthermore, stress-induced changes in circulating NPY-like immunoreactivity do not originate from the adrenal gland but mainly from the peripheral nervous system, and the release of NPY is dependent upon the nature of the stimulus.

Adrenalectomy↗

PubMed1987

Neuropeptide Y in multiple endocrine neoplasia: release during surgery for phaeochromocytoma.

High plasma concentrations of neuropeptide Y (NPY) were found in a patient with bilateral adrenal phaeochromocytomas and medullary thyroid carcinoma associated with MEN IIa (32 pmol/l, normal less than 3.5 pmol/l). Both adrenal tumours contained and secreted NPY. Manipulation at operation produced a remarkable increase in plasma NPY concentrations (peak = 1631 pmol/l) coinciding with increases in plasma levels of catecholamines and arterial pressure. NPY was also shown to be present in thyroid tumour tissue: the concentration of NPY in tumour was 50-fold higher (0.9 nmol/g vs 0.004 nmol/g) than in adjacent normal thyroid tissue. It is possible that NPY from some phaeochromocytomas may contribute to hypertension during surgery.

Adrenal Gland Neoplasms↗

PubMed1987

The actions of the peptides, neuropeptide Y and peptide YY, on the vascular and capsular smooth muscle of the isolated, blood-perfused spleen of the dog.

The two peptides, neuropeptide Y (NPY) and peptide YY (PYY) were compared for potency on the vascular and extravascular smooth muscle of the isolated, blood-perfused spleen of the dog. The only vascular response to both NPY and PYY was vasoconstriction; the maximum effect was to arrest splenic arterial blood flow completely. On a molar basis both NPY and PYY were significantly more potent (P less than 0.01) as splenic arterial vasoconstrictors than the transmitter noradrenaline (NA). PYY was approximately 7 times more potent as a vasoconstrictor than NPY. In contrast to their potency on the vascular smooth muscle, NPY and PYY were significantly (P less than 0.01) less potent than NA in causing contraction of the splenic capsule. The two peptides were equipotent in eliciting this contraction.

Animals↗