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C Pupilli

Publications and source records attributed to C Pupilli.

At least 37 records · Page 2Linked to original sources
PubMed1995

Role for endogenous dopamine in modulating sympathetic-adrenal activity in humans.

Dopamine (DA) is synthesized and secreted in central as well as peripheral nervous system and in the adrenal medulla. Neuronal DA receptors, which have been characterized as D2 receptors, mediate an inhibition of adenylate cyclase and are located prejunctionally on sympathetic nerve endings and on chromaffin cells. Their pharmacological activation causes an inhibition of in vitro and in vivo norepinephrine (NE) release from sympathetic nerve terminals and an inhibition of in vitro epinephrine (E) release from the adrenal medulla. Endogenous DA, co-secreted with the other catecholamines (CA), modulates sympathetic-adrenal discharge only during high sympathetic stimulation through an autocrine mechanism, limiting excessive sympathetic adrenal discharge. Also pheochromocytoma cells synthesize and express D2 receptors. In patients with pheochromocytoma D2 antagonists cause hypertensive crises but the mechanism mediating this effect is still unknown as well as whether endogenous DA might modulate tumoral secretion.

Adrenal Gland Neoplasms↗
PubMed1995

[Diagnostic problems in pheochromocytoma].

Pheochromocytoma is mainly characterized by a great deal of variability in its biological activity and in its clinical manifestations. This special feature has always to be taken into account in any diagnostic procedure. The tumor is generally suspected on clinical ground for the presence of paroxysmal hypertension but this sign is largely aspecific and often absent. The diagnosis of pheochromocytoma has to be based on laboratory tests demonstrating an excess and/or a disregulation in catecholamine (CA) secretion. CA or CA metabolites can be measured in urine or blood. Whatever the sample measured, it is important to correlate its result with the clinical picture found during its collection. Basal plasma CA concentrations are often raised also during periods of normotension but their accuracy is the highest in samples drawn during a hypertensive crisis. When basal measurements are insufficient for a final diagnosis, inhibitory (clonidine) or stimulatory (glucagon) tests can be performed. Clonidine test is recommended in patients showing slight increases in basal plasma CA. Glucagon stimulation test should be performed only in normotensive patients with an incidental adrenal mass, patients with sporadic hypertensive crises or members of families affected by MEN II. Localization procedures are mainly based on CT (or MRI) and on scintigraphy with I131-MIBG. CT possesses high sensitivity (about 96%) while I131-MIBG scintigraphy possesses a very high specificity (about 97%). Therefore, both the procedures should be performed before surgery. Rarely, it is also necessary to perform catheterization of the venous tree and plasma sampling for CA measurement to localize the tumor through the discovery of a secretory gradient.

3-Iodobenzylguanidine↗
PubMed1994

Presence and distribution of endothelin-1 gene expression in human kidney.

To investigate the presence and the distribution of preproendothelin-1 (prepro-ET-1) mRNA in human kidney, eight human kidneys obtained at surgery from patients affected by localized renal tumors were studied. Northern blot analysis using a human prepro-ET-1 cDNA probe labeled with 32P showed the presence of a single band of approximately 2.3 kb that was present both in the renal cortex and medulla of all the kidneys studied. Densitometric analysis of hybridization signals demonstrated that prepro-ET-1 mRNA levels in the renal medulla were 2.2-fold higher than those in the renal cortex. The distribution of prepro-ET-1 mRNA in human kidney was investigated by in situ hybridization using a human prepro-ET-1 RNA probe labeled with 35S. The greatest density of prepro-ET-1 mRNA was observed in the renal medulla, where hybridization signal was demonstrated in vasa recta bundles and capillaries and in collecting ducts. By combining in situ hybridization with immunohistochemical detection of von Willebrand factor, we demonstrated that 93 +/- 2.5% of nontubular medullary cells containing prepro-ET-1 mRNA were endothelial cells. In the cortex, prepro-ET-1 mRNA was localized in the endothelial layer of arcuate and interlobular arteries and veins and in the endothelial cells of afferent arterioles. The results of the present study demonstrate that ET-1 gene expression is present in vascular and tubular structures of the human kidney. It is possible that ET-1 synthesized locally in the human kidney represents a local system affecting renal hemodynamics and functions through paracrine and/or autocrine actions on different renal structures.

Aged↗
PubMed1994

Insulin-like growth factor-I (IGF-I) and its binding protein IGFBP-4 in human prostatic hyperplastic tissue: gene expression and its cellular localization.

It has been previously reported that 1) type I insulin-like growth factor (IGF) receptors are present in the human prostatic tissue; 2) IGF-I receptors are mainly localized in the epithelial cells; 3) IGF-I is a mitogen for prostatic epithelial cells in culture; and 4) IGF-binding proteins (IGFBPs) are released by these cells in the conditioned medium. To add information on the mechanism of IGF-I action in the human prostate, we studied the expression and cellular localization of mRNA encoding IGF-I and IGFBP-4 in human prostatic hyperplastic (BPH) tissue. Northern analysis of total RNA extracted from BPH tissues with cDNA probes containing the entire coding regions for IGF-I and IGFBP-4 documented the presence of multiple IGF-I mRNA transcripts with lengths of 7.5, 1.7, 1.3, and 1.1 kilobases and a single 2.1-kilobase transcript of IGFBP-4 mRNA. In situ hybridization with the cDNA probes used for Northern analysis and with cRNA probes synthesized from the respective cDNA demonstrated that IGF-I mRNA was only localized in the stromal cells, whereas IGFBP-4 mRNA was predominantly expressed by epithelial cells. In addition, immunoreactive IGF-I was measured in BPH tissue extracts after acidification and reverse phase chromatography. The mean (+/- SD) IGF-I content of six BPH tissues was 28.1 +/- 4.0 ng/g tissue. Our results suggest that in the human prostate, the locally secreted IGF-I exerts its principal biological effects with a paracrine mode of action and demonstrate that IGFBP-4 is mainly expressed by IGF-I target cells.

Carrier Proteins↗
PubMed1994

Adrenal medulla secretion in Cushing's syndrome.

To investigate whether chronic endogenous hypercortisolism might alter adrenomedullary phenylethanolamine N-methyltransferase activity, we measured epinephrine/norepinephrine (E/NE) ratios in the adrenal venous blood of 8 patients undergoing surgery for Cushing's syndrome and in 12 control subjects undergoing surgery for left kidney diseases. To investigate the adrenomedullary secretory activity in Cushing's syndrome, we measured basal E plasma levels in 24 patients and 32 age- and sex-matched normal control subjects, and we evaluated the adrenomedullary response to glucagon in 9 patients and in 22 age- and sex-matched normal subjects. Last, to clarify whether chronic endogenous hypercortisolism might modify E plasma levels through a modification of E metabolism, we measured the E MCR in four patients and four age-matched controls. Mean (+/- SEM) E/NE ratio in adrenal venous blood was similar in patients with Cushing's syndrome (4.61 +/- 0.78) and in the control group (4.71 +/- 0.74). Mean (+/- SEM) basal plasma E was significantly lower in patients with Cushing's syndrome (98.2 +/- 10.9 vs. 184 +/- 25.1 pmol/L, P < 0.01) than in the control group. Similarly, plasma NE also was reduced (0.75 +/- 0.09 vs. 1.10 +/- 0.07 nmol/L, P < 0.01). In patients with Cushing's syndrome the E response to glucagon was significantly reduced (P < 0.01). E MCR was almost identical in patients with Cushing's syndrome (1.48 +/- 0.10 L/min.m2) and in control subjects (1.51 +/- 0.10 L/min.m2). Our data demonstrate that: 1) chronic endogenous hypercortisolism is not able to change adrenomedullary phenylethanolamine N-methyltransferase activity and therefore the quality of adrenomedullary secretion; and 2) chronic endogenous hypercortisolism causes a decrease in basal and stimulated adrenomedullary activity without altering E MCR significantly. Therefore the adrenal medulla does not seem to play a pathogenetic role in the hypertension of Cushing's syndrome.

Adrenal Medulla↗
PubMed1994

Dopamine D2 receptor gene expression and binding sites in adrenal medulla and pheochromocytoma.

To determine whether dopamine D2 receptors are present in normal and neoplastic chromaffin tissues, 10 pheochromocytomas and 5 human adrenal glands were studied. Dopamine D2 receptor messenger ribonucleic acid corresponding to a single band of approximately 2.5 kilobases was detected in both pheochromocytoma and human adrenal gland by Northern blot analysis. D2 receptor messenger ribonucleic acid levels determined by dot blot analysis were 3.1-fold lower in human adrenal medullas than in pheochromocytomas (P < 0.001). Simultaneous Scatchard analysis of [3H]spiperone binding experiments demonstrated the presence of two different binding sites in membrane preparations from bovine adrenal medullas [R1: Kd = 0.14 nmol/L; binding capacity (Bmax) = 6.2 fmol/mg protein: R2: Kd = 16 nmol/L; Bmax = 223 fmol/mg protein]. Similarly, two binding sites were present in membrane preparations from pheochromocytomas (R1: Kd = 0.39 nmol/L; R2: Kd = 61 nmol/L]. Binding capacities were greatly variable among pheochromocytomas (R1: Bmax = 12.0-372.5 fmol/mg protein; R2: Bmax = 1,000-11,586 fmol/mg protein). The relative potencies of different compounds to displace [3H]spiperone were spiperone > domperidone > (+)-butaclamol > quinpirole > SCH 23390 in bovine adrenal medulla, and spiperone >> domperidone > quinpirole > (+)-butaclamol > SCH 23390 in pheochromocytoma. We conclude that dopamine D2 receptors are synthesized in human adrenal medulla and pheochromocytoma tissues.

Adrenal Gland Neoplasms↗
PubMed1993

A nonsecreting pheochromocytoma presenting as an incidental adrenal mass. Report on a case.

A 25 year old women presented an incidental adrenal mass which was diagnosed to be a pheochromocytoma before surgery by means of a positive 131-I-MIBG scintigraphy. Urinary vanilmandelic acid resulted repeatedly normal as well as basal plasma norepinephrine (NE), epinephrine (E) and dopamine (DA). Urinary homovannilic acid resulted in the normal range. Stimulation tests with iv glucagone, tyramine and metoclopramide evoked normal NE and E responses while a slight increase in plasma DA was observed after metoclopramide. Oral clonidine suppressed plasma catecholamines (CA) normally. Histologic and immunohistochemical studies confirmed that the tumor was a pheochromocytoma showing positivity for tyrosine hydroxylase but not for dopamine-beta-hydroxylase activity. This case is the first report on a completely asymptomatic pheochromocytoma presenting as an incidental adrenal mass which was investigated with repeated biochemical tests before surgery and demonstrates that, among the extremely variable functional attitudes of pheochromocytomas, a defect in CA synthesis and secretion is also to be included.

Adrenal Gland Neoplasms↗
PubMed1992

Distribution and content of renin and renin mRNA in remnant kidney of adult rat.

To determine whether kidney hypertrophy secondary to reduction of renal mass affects the intrarenal distribution and concentration of renin mRNA and its protein, adult male Sprague-Dawley rats were studied 4 wk after sham operation (Sham, n = 10), uninephrectomy (UNX, n = 14), or five-sixths nephrectomy (5/6 NX, n = 12). Left kidney weight-to-body weight ratio (x10(3)) was higher in 5/6 NX (6.6 +/- 0.2) than in UNX (4.5 +/- 0.2) or Sham (3.8 +/- 0.1) groups (P < 0.001). The percentage of juxtaglomerular apparatuses (%JGA) containing renin was lower in 5/6 NX (32 +/- 5) than in UNX (56 +/- 2, P < 0.001) or Sham (50 +/- 1, P < 0.05) groups. Renal renin mRNA concentrations (pg renin mRNA/microgram total RNA) detected by radiodensitometric renin mRNA dot-blot assay were lower in 5/6 NX (1.8 +/- 0.3) than in UNX (13.2 +/- 1) or Sham (14.2 +/- 1.1, P < 0.001). In situ hybridization histochemistry demonstrated that in all groups of rats renin mRNA was confined to the JGA. However, the hybridization signals (grains/JGA) were less intense in 5/6 NX (211 +/- 24) than in UNX (486 +/- 35) or Sham (541 +/- 40) groups (P < 0.001). Renal renin concentration (ng angiotensin I.mg protein-1.h-1) tended to be lower in 5/6 NX (20 +/- 15) than in UNX (44 +/- 7.8) or Sham (60.8 +/- 10) groups. In addition, plasma renin activity (ng.ml-1.h-1) was lower in 5/6 NX (3.8 +/- 0.6) than in UNX (8.8 +/- 1.8, P < 0.05) or Sham (14.3 +/- 2, P < 0.001) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1991

Molecular and cellular aspects of renin during kidney ontogeny.

The activity of the renin-angiotensin system is subjected to remarkable developmental changes. Circulating as well as renal concentrations of renin are high in early life, decreasing progressively as maturation evolves. This review summarizes the current molecular framework underlying those changes during kidney development. Evidence is presented demonstrating that expression of the renin gene is developmentally regulated. Renin messenger ribonucleic acid (mRNA) levels are higher in fetuses and newborns than in adult mammals. As maturation progresses, the distribution of renin and its mRNA shifts from large intrarenal arteries in the fetus to the classic juxtaglomerular localization in the adult. Potential explanations for these changes as well as the cytosolic events mediating renin release and gene expression are discussed. Evidence is also presented demonstrating that under diverse physiologic and pathologic conditions the adult kidney vasculature has the capability to recruit renin gene expressing and/or containing cells. Throughout, an effort has been made to identify gaps in our knowledge. Not without bias, we hope that future research in this area will lead to a better understanding of the biology of renin in the developing as well as the adult individual.

Angiotensins↗
PubMed1991

Spatial association of renin-containing cells and nerve fibers in developing rat kidney.

The development of renin-containing cells and nerve fibers was studied in Sprague-Dawley rat kidneys during the last third of gestation and the first 15 days of postnatal life. Kidney tissue sections were stained for nerve fibers or double stained employing an anti-rat renin polyclonal antibody and a monoclonal antibody (TUJ1) directed against a neuron-specific class III beta-tubulin isotype. Renin-containing cells and nerve fibers were detected at 17 days of gestation, in close spatial relationship along the main branches of the renal artery. During fetal life, renin-containing cells and nerve fibers were spatially associated along arcuate and interlobular arteries, renin-containing cells being also present throughout the entire length of afferent arterioles supplying juxtamedullary glomeruli. During postnatal life the distribution of renin-containing cells progressively shifted to a restricted juxtaglomerular position in afferent arterioles. Simultaneously, density and organization of nerve fibers increased with age along the arterial vascular tree. Our results suggest that innervation of renin-containing cells is present in fetal life and follows the centrifugal pattern of renin distribution and nephrovascular development.

Animals↗
PubMed1990

Dopamine modulation of pathological human chromaffin tissue.

To evaluate the presence of dopamine-2(DA2) binding sites in pheochromocytoma tissue, we performed binding studies and light microscopy autoradiography on sections of 7 different tumors. 3-H-Spiroperidol, a DA2 ligand, bound specifically to tumor sections with a (mean +/- SD) Kd value of 1.93 +/- 0.62 nmol/L. Binding site density (Bmax) was 29.16 +/- 2.33 fmol/mg tissue. Light microscopy autoradiography showed a nonhomogenous localization of silver grains within chromaffin cells. The specific binding was about 50% of total. To investigate whether DA2 binding sites found on pheochromocytoma cells might modulate catecholamine (CA) release, we studied the effects of oral bromocriptine (2.5 mg) on circulating CA of 5 patients with pheochromocytoma. In these patients bromocriptine caused a decrease in blood pressure (P less than .05) but no significant change in plasma CA. Our study shows the presence of DA2 binding sites on tumoral chromaffin tissue. As bromocriptine, a DA2 receptor agonist, was not able to modify tumor CA secretion, the functional role, if any, played by these binding sites on tumor secretion is still to be clarified.

Adrenal Gland Neoplasms↗
PubMed1990

Dopaminergic modulation of human adrenal medulla: indirect evidence for the involvement of DA-2 receptors located on the chromaffin cells.

1. Pharmacological blockade of DA-2 receptors causes a significantly higher epinephrine (E) response to physical exercise in normal man. 2. The present study was undertaken to evaluate whether dopaminergic modulation of E secretion is present also for a stimulus such as glucagon which acts directly on chromaffin cells. 3. Seven normal males were studied in a single blind randomized manner on two separate occasions, after pre-treatment with placebo or domperidone (DMP; 20 mg orally). Plasma E and norepinephrine, plasma prolactin, heart rate and blood pressure were measured on two separate occasions (placebo vs DMP) before and after a glucagon (1 mg i.v.) stimulation test. 4. Glucagon caused an increase in plasma E either after placebo (P = 0.043) or after domperidone (P = 0.012). DMP administration caused a significant increase in plasma E (P = 0.0008). Absolute increase in plasma E after glucagon was significantly higher after DMP than after placebo (P = 0.030). 5. As the dopaminergic modulation of human adrenal medulla is confirmed also for a stimulus acting directly on chromaffin cells, the results of the present study suggest that the DA-2 receptors responsible for the modulation are located on medullary cells.

Adrenal Medulla↗
PubMed1990

Catecholamines and blood pressure regulation.

Catecholamines (CAs) play a central role in the regulation of blood pressure. Sympathetic adrenal effects are ultimately elicited by the neurotransmitter norepinephrine and the hormone epinephrine. Their release is under the control of higher centers and is finely modulated by several factors such as presynaptic receptors. Recent evidences suggest that also the peripheral dopaminergic system can participate in blood pressure regulation intervening in the blood flow regulation of some regions, and in sodium-water balance. The measurement of CAs in biological fluids has greatly enhanced our knowledge on the mechanisms regulating blood pressure and is widely applied in cardiovascular research. Clinical applications of CA measurement are still limited to the diagnosis of pheochromocytoma and to the differential diagnosis of hypotensive syndromes.

Adrenal Gland Neoplasms↗
PubMed1988

Presence of dopamine-dependent adenylate cyclase activity in human renal cortex.

The effects of dopamine (DA) and of two selective DA DA1 agonists (SKF 38393 and SKF 82526) on adenylate cyclase activity were studied with human kidney cortex membrane preparations. DA elicited a dose-related stimulation of adenylate cyclase activity with an EC50 of 60 microM. The selective DA DA1 antagonist SCH 23390 behaved as a competitive antagonist, shifting the dose-response curve to the right. The non-selective beta-adrenoceptor antagonist (-)-propranolol did not affect the EC50 of the dose-response curve to DA but attenuated the maximal stimulatory effect of DA at concentrations higher than 100 microM. (+)-Sulpiride inhibited DA-induced adenylate cyclase stimulation in a dose-dependent manner with an IC50 of 4.6 X 10(-8) M but (-)-sulpiride was without effect. Both SKF 38393 and SKF 82526 stimulated the adenylate cyclase activity of human kidney cortex; this effect was completely antagonized by SCH 23390. Our results, demonstrating the presence of DA-sensitive adenylate cyclase activity, strongly suggest the presence of a DA receptor of the DA1 subtype in human kidney cortex.

Adenylyl Cyclases↗
PubMed1988

Measurement of catecholamines, met-enkephalin, somatostatin and substance P-like immunoreactivities in 12 human pheochromocytomas.

The present study was designed to evaluate the simultaneous presence of epinephrine (E), norepinephrine (NE), met-enkephalin (ME)-, somatostatin (SRIF)- and substance P (SP)- like immunoreactivities (LI) in extracts of 12 pheochromocytomas obtained at the time of surgery from 10 patients. Moreover, catecholamines and ME-LI levels were measured in peripheral plasma of each patient. Each pheochromocytoma was characterized by a high variability of ME-LI, SRIF-LI, SP-LI, E and NE levels. The highest E concentrations were found in tumors from patients with Multiple Endocrine Adenomatosis (MEA) IIa syndrome, whereas in sporadic pheochromocytomas NE was the main catecholamine. Among the neuropeptides ME-LI showed the highest intratumoral concentration, and SP-LI the lowest. No correlations were found between intratumoral levels of catecholamines and any of the neuropeptides or between any of the different neuropeptides measured. Plasma catecholamine levels were not correlated with intratumoral catecholamine levels. Plasma ME-LI was higher than normal in only one patient. No correlation was observed between tumoral CA or peptide content and the clinical picture. Our study confirms that human pheochromocytoma cells can synthetize different neuropeptides. The variability of the clinical picture very likely depends on the biochemical and biological heterogeneity of this chromaffin tumor.

Adrenal Gland Neoplasms↗
PubMed1988

Endogenous dopamine (DA) and DA2 receptors: a mechanism limiting excessive sympathetic-adrenal discharge in humans.

We studied the effects of presynaptic dopamine (DA) 2 receptor blockade on the sympathetic-adrenal response to graded exercise in seven normal men. DA2 receptor blockade was achieved by means of domperidone (DMP) administration. The exercise consisted of progressive cycling activity, from 30-80% of the predetermined maximal oxygen consumption for each man. Systolic, diastolic, and mean arterial pressures; heart rate; and plasma norepinephrine (NE), epinephrine (E), PRL, glucose, lactate, FFA, sodium, potassium, cortisol, and PRA were measured at rest, during exercise, and during recovery after placebo or DMP administration. Graded exercise caused significant increases in systolic and mean arterial pressures and plasma NE, E, lactate, sodium, potassium, FFA, cortisol, and PRA. DMP administration before exercise caused a significant increase in plasma PRL (P = 0.0009), a greater increase in plasma NE at the end of the exercise (P = 0.002), and an overall increase in plasma E (P = 0.02) and FFA (P = 0.02) concentrations. These results strongly suggest that endogenous DA limits catecholamine release during sympathetic-adrenal stimulation by activating DA2 receptors.

Adrenal Glands↗
PubMed1987

Usefulness of basal catecholamine plasma levels and clonidine suppression test in the diagnosis of pheochromocytoma.

In the present paper we report our experience on the utility of basal plasma catecholamine (CA) measurement and of the clonidine-suppression test in the diagnosis of pheochromocytoma. Basal noradrenaline (NA) and adrenaline (A) were assayed in plasma samples of 27 subjects affected by pheochromocytoma. When compared to basal values obtained in hypertensive patients without pheochromocytoma, one or both the CA resulted pathologically elevated in all patients except one. The response to the clonidine-suppression test was evaluated in 41 hypertensive patients suspected of having a pheochromocytoma measuring plasma NA and A in basal conditions and 2 and 3 h after oral administration of 300 micrograms clonidine. Extensive laboratory and instrumental findings confirmed the presence of pheochromocytoma only in 12 patients. Among the other 29 patients basal plasma CA resulted higher than normal in 4 patients. In patients without pheochromocytoma clonidine induced a significant fall in both NA and A plasma levels. The decrease in NA was observed in each patient. The 12 patients with pheochromocytoma showed a pathological elevation of one or both the CA. In this group clonidine did not significantly suppress plasma CA. The individual responses were extremely variable. Our data confirm the validity of plasma CA measurement as a diagnostic tool for the diagnosis of pheochromocytoma. The results of the clonidine-suppression test were generally confirmatory of the basal CA plasma values but in the 4 hypertensive patients without pheochromocytoma who showed basal plasma CA higher than normal clonidine resulted a useful tool in excluding the presence of pheochromocytoma.

Adolescent↗