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P Persson

Publications and source records attributed to P Persson.

At least 55 records · Page 3Linked to original sources
PubMed1992

Determination of 4,4'-methylenedianiline in hydrolysed human urine by micro liquid chromatography with ultraviolet detection.

4,4'-Methylenedianiline was determined in human urine by micro liquid chromatography with ultraviolet detection. The combination of a thorough work-up and the high mass sensitivity of micro liquid chromatography gave the method very high sensitivity. Derivatization with pentafluoropropionic anhydride enhanced the resolution of the 4,4'-dimethylenedianiline peak. The detection limit, defined as blank plus three times the standard deviation of the blank, was 2 nmol/l of urine, for 10-microliters injection volumes. The detection limit, defined as three times the noise, was about ten times better. The within- and between-assay coefficients of variation were 4 and 6%, respectively, for samples containing 40 nmol/l. The method was applied for the monitoring of excreted 4,4'-methylenedianiline in urine, during epicutaneous skin hypersensitivity testing (patch testing).

Aniline Compounds↗
PubMed1991

Canine hydrophobic surfactant polypeptide SP-C. A lipopeptide with one thioester-linked palmitoyl group.

The amino acid sequence and the posttranslational modification of the hydrophobic surfactant polypeptide SP-C from canine, rabbit and bovine lungs were established by direct sequence analysis and plasma-desorption time-of-flight mass spectrometry. The results reveal that canine SP-C has only one cysteine residue which, however, is palmitoylated, like the two Cys residues in other characterized SP-C molecules. In addition, canine SP-C is N-terminally truncated, with only 34 amino acid residues in its longest form. Thus, SP-C molecules can apparently vary to some extent in the N-terminal lipid-modified part, whereas the extremely hydrophobic middle and C-terminal parts are well conserved.

Amino Acid Sequence↗
PubMed1991

Thrombin and H64A subtilisin cleavage of fusion proteins for preparation of human recombinant parathyroid hormone.

Human parathyroid hormone, hPTH, an 84 amino acid polypeptide, was produced intracellularly in Escherichia coli as a fusion protein, linked to the C-terminus of a 15 kD IgG-binding protein. Approximately 100 mg fusion protein was obtained per liter fermentation medium. To test the efficiency of two alternative enzymatic cleavage methods, two fusion proteins differing only in the linker region were constructed. Cleavage of a Phe-Phe-Pro-Arg linker was obtained with bovine thrombin and cleavage of a Phe-Ala-His-Tyr linker with recombinant H64A subtilisin. Both enzymes yielded the correct N-terminus and cleaved their respective linkers quantitatively, although additional internal cleavage sites in hPTH were detected and characterized. The linker cleavage conditions were optimized and hPTH was purified to homogeneity. Thrombin cleavage resulted in a final yield of 5 mg hPTH/L, while H64A subtilisin cleavage was more specific and gave 8 mg/L. The purified recombinant product was identical to native hPTH and exhibited full biological activity in an adenylate cyclase assay.

Amino Acid Sequence↗
PubMed1991

Importance of the stomach in maintaining calcium homoeostasis in the rat.

The stomach helps to maintain calcium homoeostasis by making dietary calcium accessible for uptake in the intestines, although the effect of the stomach on calcium homoeostasis is poorly understood. We examined the effect on blood calcium of gastric surgery in the rat. Within three weeks gastrectomy and fundectomy (excision of the acid producing part of the stomach) induced a slight lowering of the blood calcium concentration. When parathyroidectomy was combined with either gastrectomy or fundectomy the blood calcium concentrations promptly dropped to values lower than after parathyroidectomy alone. The mortality was close to 100% during the first three weeks after combined parathyroidectomy and gastric surgery. It was nil in rats subjected to parathyroidectomy alone. Gastrectomised rats absorbed Ca2+ better than unoperated control rats, possibly reflecting the fact that the serum 1,25-dihydroxyvitamin D concentration was raised. Gastrectomised rats had a food intake that was about 70% of that in intact rats, and the amount of dietary calcium absorbed (net absorption per kg body weight) by the gastrectomised rats was approximately 65% of that in intact control rats. We conclude that the acid producing part of the stomach is important for calcium homoeostasis, since its removal induced lethal hypocalcaemia in parathyroidectomised rats. One possible explanation for the hypocalcaemia induced by gastrectomy is a progressive calcium deficit. In addition, the loss of calciotrophic hormones originating in the stomach may contribute.

Animals↗
PubMed1991

Effects of gastrin on calcium homeostasis in chickens.

As in the rat, gastrin and an extract of the acid-producing part of the stomach (proventriculus) were found to lower the blood Ca2+ concentration in the chicken. Furthermore, gastrin enhanced the uptake of 45Ca into the femur. It has been suggested previously that gastrin causes hypocalcemia in the rat by releasing gastrocalcin, a hypothetical hormone thought to reside in the acid-producing part of the stomach. The results of the present study in the chicken are in agreement with this concept. Not only exogenous, but also endogenous gastrin lowered blood calcium levels. Thus, the serum gastrin concentration was increased in response to ranitidine-evoked blockade of the gastric acid output; the rise in gastrin was associated with a transient drop in blood calcium. Also, food intake produced a rise in the serum gastrin concentration and a transient drop in blood calcium. However, injection of ranitidine or food intake in proventriclectomized (acid-producing part of the stomach extirpated) chickens failed to lower blood calcium, supporting the view that the gastrin-evoked hypocalcemia depends upon an agent in the gastric (proventriculus) mucosa. We suggest that endogenous and exogenous gastrin evoke hypocalcemia in the chicken by the same mechanism as that which has been postulated in the rat, i.e. by mobilization of the candidate hormone gastrocalcin from endocrine cells in the acid-producing gastric mucosa.

Animals↗
PubMed1990

Elevated serum gastrin after food intake or acid blockade evokes hypocalcemia.

Gastrin lowers blood Ca2+ in the rat. Recently, it was suggested that gastrin causes hypocalcemia by releasing gastrocalcin, a hypothetical peptide hormone thought to reside in the acid-producing part of the stomach. The results of the present study suggest that not only exogenous gastrin but also gastrin of endogenous origin lowers blood Ca2+. Food intake in fasted intact rats produced a transient drop in blood Ca2+, probably induced by the postprandial rise in serum gastrin. Food intake in fasted gastrectomized or fundectomized (acid-producing part extirpated) rats failed to induce any lowering of the blood Ca2+, supporting the view that the gastrin-evoked hypocalcemia is dependent upon a factor in the oxyntic mucosa. Also, the increase in serum gastrin concentration following intraperitoneal injection of the histamine H2-receptor antagonist ranitidine was associated with a drop in blood Ca2+ and also the ranitidine-evoked hypocalcemia could be prevented by gastrectomy. We suggest that endogenous gastrin evokes hypocalcemia by the same mechanism as exogenous gastrin, i.e., by mobilization of gastrocalcin from the acid-producing part of the stomach.

Animals↗
PubMed1990

Evidence that gastrin enhances 45Ca uptake into bone through release of a gastric hormone.

An acute challenge with gastrin-17 enhanced the uptake of 45Ca into sternum and several long bones in rats by about 10-30%; gastrectomy prevented this effect. Long-term treatment with (Leu15)-gastrin-17 (continuous infusion via osmotic minipumps for 4 weeks) enhanced the uptake of 45Ca into bone (examplified by radius and sternum) by 18-26% (tested on the last day of the infusion). Surgical removal of the acid-producing part of the stomach (fundectomy) or treatment with the anti-ulcer drugs, ranitidine (a histamine H2-receptor antagonist administered by continuous infusion) or omeprazole (an H+/K(+)-ATPase inhibitor administered daily by gastric tube for 4 weeks), induced sustained hypergastrinemia (through loss of acid feedback inhibition of gastrin release). The ranitidine- and omeprazole-evoked hypergastrinemia was associated with 32-62% enhancement of bone 45Ca uptake but the hypergastrinemia of fundectomized rats was not. Gastrectomy abolished the effect of omeprazole. We suggest that exogenous and endogenous gastrin influences calcium uptake into bone indirectly by releasing a calciotropic hormone (gastrocalcin) from the acid-producing part of the stomach. The bone ash weight was reduced by gastrectomy or fundectomy (4 weeks), but neither ranitidine nor omeprazole-evoked hypergastrinemia (4 weeks) raised the bone ash weight. The stimulated calcium uptake into bone of hypergastrinemic rats treated with ranitidine or omeprazole was associated with a 22-32% increase in the density of osteoclasts in the tibia. This finding is in line with the hypothesis that long-lasting hypergastrocalcinemia produces accelerated turn-over of bone rather than increased bone calcium content.

Animals↗
PubMed1990

Hydrophobic surfactant-associated polypeptides: SP-C is a lipopeptide with two palmitoylated cysteine residues, whereas SP-B lacks covalently linked fatty acyl groups.

Pulmonary surfactant contains two hydrophobic polypeptides, SP-B and SP-C, with known amino acid sequences and with truncated subforms lacking the N-terminal residues. Treatment of SP-C with KOH releases fatty acids (palmitic acid to more than 85%) in molar ratios of 1.8-2.0 relative to the polypeptide. Furthermore, plasma-desorption mass spectrometry shows native SP-C of both the intact and truncated types to be monomers with masses about 500 units higher than those expected for the polypeptide chains. After treatment with KOH, trimethylamine, or dithioerythritol, the polypeptide masses are obtained. These results prove that native SP-C is a lipopeptide with two palmitoyl groups covalently linked to the polypeptide chain. The deacylation conditions, the presence of two cysteine residues in the polypeptide, and the absence of other possible attachment sites establish that the palmitoyl groups are thioester-linked to the two adjacent cysteine residues. In contrast, the major form of porcine SP-B is a dimer without fatty acid components. That SP-C is a true lipopeptide with covalently bound palmitoyl groups suggests possibilities for functional interactions. It gives a direct physical link between SP-C and surfactant phospholipid components. Long-chain acylation may constitute a means for association of proteins with membranes and could conceivably modulate the stability and biological activity of surfactant films.

Amino Acid Sequence↗
PubMed1989

Sympathetic modulation of renal hemodynamics, renin release and sodium excretion.

In anesthetized animals it has been shown previously, that the influence of electrical stimulation of efferent renal nerves on renal function with increasing stimulation frequencies can be graded; renin release is affected at low, sodium excretion at intermediate and vascular resistance at high stimulation frequencies. Experiments in conscious dogs are reviewed, which present evidence for a similar functional dissociation under physiological conditions. Moderate activations of the renal sympathetic nerves, which do not change renal blood flow 1) decrease sodium excretion independent of changes in angiotensin II, 2) interact with the pressure-dependent mechanism of renin release by resetting its threshold pressure and 3) modulate autoregulation by increasing the lower limits of glomerular filtration rate and renal blood flow-autoregulation. These findings may contribute to our understanding of the role of the renal nerves in the pathophysiology of congestive heart failure and hypertension.

Animals↗
PubMed1989

Resetting of pressure-dependent renin release by intrarenal alpha 1-adrenoceptors in conscious dogs.

We investigated the influence of a stimulation of intrarenal alpha 1-adrenoceptors on the relationship between renin release and renal artery pressure in 8 conscious, chronically instrumented dogs receiving a normal salt diet. Renin stimulus-response curves were determined by a stepwise reduction of renal artery pressure down to 70 mm Hg (1) under control conditions, (2) during a bilateral common carotid occlusion combined with an intrarenal prazosin infusion, and (3) during an intrarenal methoxamine infusion. Both drug infusions did not alter resting renal blood flow. (1) The control renin stimulus-response curve revealed a flat portion (plateau-level) around and above the resting blood pressure and a very steep portion (slope) below a well-defined threshold pressure 10-15 mm Hg below the resting blood pressure. (2) An intrarenal alpha 1-adrenoceptor blockade by prazosin prevented the resetting of the threshold pressure which is regularly observed during bilateral common carotid occlusion. (3) An intrarenal infusion of the alpha 1-adrenoceptor agonist methoxamine increased the threshold pressure. We suggest that the neural control of renin release within the autoregulatory range of renal blood flow involves two independent mechanisms: the direct release of renin from juxtaglomerular granular cells by beta 1-adrenoceptors, and the modulation of the threshold pressure of pressure-dependent renin release by intrarenal alpha 1-adrenoceptors. The small changes in renal nerve activity necessary to reset the threshold pressure and the close relationship between the threshold pressure and resting blood pressure imply an important function of intrarenal alpha 1-adrenoceptors in the regulation of renin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1989

Helodermin-like peptides in noradrenaline cells of adrenal medulla.

Helodermin, a VIP/secretin-like peptide, was first isolated from the venom of the lizard Gila monster. Small amounts of helodermin-like peptides have since been detected in many mammalian tissues. Notably high concentrations were demonstrated in the thyroid gland, and immunocytochemical studies revealed intense helodermin-like immunostaining in thyroid C cells and medullary thyroid carcinoma cells. In the present study, we examined the adrenal gland of mouse, rat and pig for the presence of helodermin-like peptides. Using an antiserum raised against lizard helodermin immunostaining was observed in the noradrenaline-producing cells of the adrenal medulla in all 3 species. Radioimmunoassay revealed high concentrations of helodermin-like peptides in the mouse and rat adrenal. The concentrations in the pig adrenal could not be determined because of a non-parallel dilution curve. Upon high-performance liquid chromatography, the immunoreactive material in extracts of mouse and rat adrenals eluted in one major peak, close to the elution position of lizard helodermin.

Adrenal Medulla↗
PubMed1989

Helodermin-like peptides in thyroid C cells: stimulation of thyroid hormone secretion and suppression of calcium incorporation into bone.

Helodermin is a vasoactive intestinal peptide-like peptide in the salivary gland venom of the lizard Heloderma suspectum. Helodermin-like immunofluorescence was observed in the parafollicular (C) cells in several mammals and in the C cell homologues of the chicken ultimobranchial gland. Thus, helodermin-like peptides coexist with calcitonin. The results of radioimmunoassay agreed with the immunocytochemical findings. HPLC of rat thyroid extracts revealed one major peak of helodermin-like immunoreactivity, which eluted in a position close to that of lizard helodermin. Helodermin stimulated basal thyroid hormone secretion and colloid droplet formation in conscious mice. The effect of large doses of helodermin was quite long-lasting and the maximal response occurred after 2-6 hr. In addition, helodermin suppressed the incorporation of calcium into bone in conscious rats. The findings suggest that helodermin-like peptides in C cells may be involved in the local regulation of thyroid hormone secretion and in the maintenance of calcium homeostasis.

Animals↗
PubMed1989

Gastrin releases a blood calcium-lowering peptide from the acid-producing part of the rat stomach.

Gastrin-17 induces hypocalcemia in the rat without stimulating calcitonin release. The gastrin-induced hypocalcemia persisted after thyroparathyroidectomy or parathyroidectomy. In contrast, gastrectomy or extirpation of the acid-producing part of the stomach prevented the hypocalcemic effect, suggesting the involvement of the proximal stomach in the gastrin-evoked lowering of blood calcium. The drop in blood calcium upon injection of gastrin-17 did not reflect a loss of calcium via the gastric juice or via the urine. Extracts of the acid-producing mucosa of the rat stomach had a hypocalcemic effect. The extracts were purified by gel chromatography and reversed-phase high-performance liquid chromatography. Digestion with leucine aminopeptidase destroyed the hypocalcemic activity, while trypsin had no effect, suggesting a peptide (or peptides) with an unprotected NH2 terminus and without basic amino acid residues (or with protected basic amino acids). Both gastrin-17 and the mucosal extract stimulated the uptake of 45Ca into bone (radius and sternum). Gastrin-17 was without effect in rats that had undergone gastrectomy, while the mucosal extract was equally effective in gastrectomized and unoperated rats. We suggest that the effects of gastrin-17 on blood calcium and on calcium transfer into bone are indirect and that gastrin-17 stimulates the release of a peptide hormone, tentatively named gastrocalcin, from the acid-producing mucosa of the stomach. Gastrocalcin stimulates the uptake of 45Ca into bone, thereby causing hypocalcemia.

Animals↗
PubMed1989

ANP and sodium excretion during acute baroreflex hypertension in conscious dogs.

The influence of an acute baroreflex hypertension elicited by common carotid occlusion (CCO) on plasma atrial natriuretic peptide (ANP) and renal sodium excretion was investigated in chronically instrumented, conscious foxhounds receiving a normal-sodium diet. CCO (n = 6) significantly increased mean arterial pressure (from 102 +/- 5 to 144 +/- 3 mmHg; P less than 0.01) and sodium excretion (from 82 +/- 10 to 133 +/- 9 mumol/min; P less than 0.05). No changes in plasma ANP and right atrial pressure were observed during the acute hypertension. In contrast, an acute 20% volume expansion (n = 7) corresponding to 1.8% of body weight raised right atrial pressure (from 1.3 +/- 1.2 to 5.8 +/- 1.2 cmH2O; P less than 0.01) and induced a sustained elevation of plasma ANP (from 39 +/- 8 to 67 +/- 16 pg/ml; P less than 0.05). The natriuresis in response to CCO was eliminated when renal perfusion pressure was regulated at the control level by a renal arterial cuff (n = 4); under these conditions, sodium excretion even tended to decrease during CCO (from 81 +/- 17 to 46 +/- 13 mumol/min; P less than 0.05). In conclusion, an increase in renal perfusion pressure and not an elevated ANP level is important in mediating the natriuresis during CCO in conscious dogs. These results imply that changes in plasma ANP are not essential for the induction and maintenance of a pressure natriuresis.

Acute Disease↗
PubMed1988

Physiology of the renal baroreceptor mechanism of renin release and its role in congestive heart failure.

The function of the renal baroreceptor can be quantitatively described by a stimulus-response curve showing a flat section in the high pressure range, a steep slope in the low pressure range, and a well-defined threshold pressure slightly below resting systemic pressure. This stimulus-response curve shows a close functional relation to autoregulation of renal blood flow, glomerular filtration rate and sodium excretion. Threshold pressure and slope are subject to different physiologic control mechanisms: The slope is increased by a low sodium diet, whereas threshold pressure is elevated by an increased renal sympathetic nerve discharge or by circulating catecholamines. Sympathetic influences also reset renal autoregulation. Recent studies have provided evidence for an important role of the renal baroreceptor in the long-term control of arterial blood pressure. The sympathetic modulation of threshold pressure can induce sodium retention in early heart failure, and the sympathetic effects on autoregulation may help to explain clinical reports on a deterioration of renal function during converting-enzyme therapy.

Animals↗
PubMed1988

Effect of sino-aortic denervation in comparison to cardiopulmonary deafferentiation on long-term blood pressure in conscious dogs.

The isolated and combined influence of cardiopulmonary and sinoaortic denervation on long-term blood pressure (MAP), heart rate (HR), plasma renin activity (PRA) and plasma volume (PV) was studied in 11 conscious, chronically instrumented foxhounds receiving a normal sodium diet. MAP, HR, PV and PRA remained unchanged in the 5 dogs after bilateral thoracic vagal stripping, which eliminates the cardiopulmonary afferents. After sino-aortic denervation in another 5 dogs there was equally little change when compared to the control group. Only total baroreceptor and cardiopulmonary denervation (7 dogs) revealed significantly higher levels of MAP (119.6 +/- 4.6 vs. 100.4 +/- 1.5, P less than 0.01), HR (118.2 +/- 3.7; vs. 84.1 +/- 3.5; P less than 0.0001), and PRA (3.6 +/- 0.9 vs. 0.9 +/- 0.2; P less than 0.05). In conclusion, the function of either arterial baroreceptors or cardiopulmonary receptors is sufficient for normal circulatory control. When both groups of receptor afferents are interrupted, MAP, HR, and PRA rise to significantly higher levels. Thus, both systems interact in a sense of a non-additive attenuation on "cardiovascular centres". This may clarify previous disputes concerning neurogenic hypertension, and supplies information for the role of the renin-angiotensin system in blood pressure control.

Afferent Pathways↗