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C Patrono

Publications and source records attributed to C Patrono.

At least 91 records · Page 5Linked to original sources
PubMed1993

In vivo expression of mutant preproendothelins: hierarchy of processing events but no strict requirement of Trp-Val at the processing site.

Endothelin-1 (ET-1), a 21-residue vasoconstrictor peptide, originates in human cells from a 212-amino acid precursor (preproET-1). Big ET-1, an intermediate form of 38 amino acids, is generated by cleavage at basic-pair residues of proET-1, while a specific "ET-converting enzyme" was proposed to process the unusual Trp-Val site at positions 21 and 22 of big ET-1. We have previously shown that expression of synthetic RNA encoding human preproET-1 in Xenopus oocytes results in secretion of putative ET-1 and big ET-1. Here, to further dissect the processing pathway of preproET-1, we designed and expressed in oocytes a set of preproET-1 mutants. Four mutants affecting the Trp-Val site always originated putative ET-1(s) at levels comparable to the wild type, suggesting that there is only a conformational requirement for cleavage at this site. An Arg-->Ile mutation at the basic-pair site after the C terminus of big ET-1 fully inhibited the formation of both big ET-1 and ET-1, indicating that processing at this site is an early event and that big ET-1 is an obligate intermediate for the synthesis of ET-1 in vivo. Also, a truncated mutant bearing a stop codon after the C terminus of the big ET-1 sequence was totally stable and further processed into mature big ET-1 and ET-1, indicating that the second part of the precursor is not necessary for maturation.

Amino Acid Sequence↗
PubMed1993

Differential effects of leukotriene C4 on endothelin-1 and prostacyclin release by cultured vascular cells.

Nanomolar concentrations of leukotriene C4 and phorbol 12-myristate acetate, a protein kinase C activator, stimulated endothelin-1 release by vascular endothelial but not smooth muscle cells. For both agonists, attenuation of this stimulatory effect was observed at higher concentrations, concomitant with but independent of enhanced prostacyclin biosynthesis.

6-Ketoprostaglandin F1 alpha↗
PubMed1993

Aspirin, but not heparin, suppresses the transient increase in thromboxane biosynthesis associated with cardiac catheterization or coronary angioplasty.

OBJECTIVES: We sought to study the dose dependence of in vivo suppression by aspirin of enhanced thromboxane biosynthesis in the setting of coronary angioplasty and to evaluate the effects of heparin and aspirin during cardiac catheterization. BACKGROUND: Percutaneous transluminal coronary angioplasty induces a controlled injury of the intima of the diseased arterial segment, with rapid deposition of platelets at the site of dilation. Thus, it provides a clinical model of intracoronary platelet activation. METHODS: The urinary excretion of a major enzymatic metabolite of thromboxane A2, 11-dehydro-thromboxane B2, was measured in 57 patients with stable coronary artery disease undergoing cardiac catheterization (n = 28) or elective single-vessel percutaneous transluminal coronary angioplasty (n = 29). Three consecutive urine collections were obtained from all patients before during and after either procedure. Patients undergoing catheterization were treated with the following regimens: a) no aspirin for > or = 10 days and no heparin (n = 12); b) no aspirin for > or = 10 days but heparin, 10,000 IU, at the time of catheterization (n = 5); c) aspirin, 300 mg/day, for at least 5 days (n = 11). Patients undergoing coronary angioplasty were randomly assigned to short-term treatment with aspirin given as a) 75 mg/day for > or = 5 days before angioplasty (n = 11); b) 300 mg/day for > or = 3 days before angioplasty (n = 9); or c) 300 mg/day for > or = 3 days before angioplasty followed by 1,000 mg during angioplasty (n = 9). RESULTS: In patients undergoing catheterization, urinary 11-dehydro-thromboxane B2 excretion (pg/mg creatinine) increased from 563 +/- 481 (mean +/- SD) to 1,684 +/- 1,332 in the absence and from 620 +/- 191 to 1,588 +/- 597 in the presence of heparin. No increase was observed in the group receiving aspirin (from 240 +/- 141 to 215 +/- 115). In patients undergoing coronary angioplasty treated with aspirin, 75 mg/day, urinary 11-dehydro-thromboxane B2 averaged 180 +/- 112, 223 +/- 178 and 294 +/- 260, respectively, before, during and after the procedure. At 300 mg/day, the corresponding values were 185 +/- 48, 217 +/- 70 and 197 +/- 93. In patients also receiving aspirin, 1,000 mg, during angioplasty, 11-dehydro-thromboxane B2 averaged 151 +/- 66, 138 +/- 43 and 133 +/- 77, respectively. CONCLUSIONS: Enhanced thromboxane biosynthesis associated with cardiac catheterization or coronary angioplasty can be largely suppressed by low dose aspirin. This finding is consistent with the view that this alteration reflects platelet activation.

Aged↗
PubMed1993

Pharmacologic modulation of the autonomic nervous system in the prevention of sudden cardiac death. A study with propranolol, methacholine and oxotremorine in conscious dogs with a healed myocardial infarction.

OBJECTIVES: The goal of the present study was to evaluate the antifibrillatory and hemodynamic effects of pharmacologic muscarinic activation and to compare them with those of beta-adrenergic blockade. BACKGROUND: Recent studies suggest a correlation between increased vagal activity and a reduced incidence of sudden cardiac death. Electrical stimulation of the vagus nerve reduces the incidence of ventricular fibrillation in a conscious animal model of sudden cardiac death. METHODS: Eleven dogs with healed anterior myocardial infarction, in which a 2-min left circumflex coronary artery occlusion during exercise caused ventricular fibrillation, were studied. They underwent subsequent tests with saline solution, propranolol (1 mg/kg body weight), methacholine (0.5 microgram/kg per min) and oxotremorine (8 micrograms/kg). RESULTS: In the test with saline solution, 100% of the dogs developed ventricular fibrillation; this occurred in only 10% of the tests with propranolol (95% confidence interval 0.2% to 44%; p < 0.001), 60% of the tests with methacholine (95% confidence interval 26% to 88%, p = 0.05) and 37.5% of the tests with oxotremorine (95% confidence interval 8% to 75%, p = 0.005). Propranolol and oxotremorine significantly reduced heart rate compared with saline solution, whereas methacholine did not. Propranolol significantly reduced maximal first derivative of left ventricular pressure, (dP/dtmax), particularly during myocardial ischemia, compared with the other treatments (2,391 +/- 582 mm Hg/s [mean +/- 1 SD] with propranolol vs. 4,226 +/- 1,237, 4,922 +/- 584 and 4,358 +/- 1,109 mm Hg/s with saline solution, methacholine and oxotremorine, respectively, p < 0.005). CONCLUSIONS: Propranolol was extremely effective against ventricular fibrillation. Methacholine and oxotremorine provided a significant, although less marked, protection and caused much less impairment of contractility compared with propranolol. Muscarinic receptor activation may represent a new approach to prevention of sudden cardiac death, particularly when beta-blockers are contraindicated and negative inotropic effects are to be avoided.

Animals↗
PubMed1993

Inhibition of thromboxane biosynthesis and platelet function by indobufen in type II diabetes mellitus.

Indobufen is a reversible inhibitor of platelet prostaglandin G/H-synthase. To verify the dose dependence of the antiplatelet effect of indobufen on ex vivo and in vivo indexes of thromboxane (TX) biosynthesis and TXA2-dependent platelet function, we studied nine patients with non-insulin-dependent diabetes mellitus (NIDDM). This was a randomized, double-blind, crossover study in which each patient was treated with three different daily regimens (50 mg BID, 100 mg BID, and 200 mg BID) of indobufen for 1 week, with a 7-day washout period between treatments. Urinary 11-dehydro-TXB2 excretion averaged 58.2 +/- 21.8 ng/h at baseline. TX metabolite excretion was reduced dose dependently by indobufen: by 67% at 50 mg BID, 72% at 100 mg BID, and 81% at 200 mg BID. Platelet cyclooxygenase activity, ATP release, collagen-induced platelet aggregation, and bleeding time also were modified dose dependently by indobufen. Biochemical demonstration of suppressed platelet TXA2 in vivo was accompanied by evidence of inhibited platelet function as assessed ex vivo. Under pathophysiological conditions, such as NIDDM, which are associated with enhanced TXA2 synthesis, more than 95% suppression of platelet cyclooxygenase activity may be necessary to produce virtually maximal inhibition of platelet TXA2 biosynthesis in vivo.

Aged↗
PubMed1993

Increased thromboxane biosynthesis in patients with acute cerebral ischemia.

BACKGROUND AND PURPOSE: Clinical and experimental studies suggest that platelets have a major role in the pathogenesis of cerebral ischemia. However, ex vivo both platelet aggregation studies and measurements of platelet-derived products in patients with cerebral ischemia have shown inconsistent results. The present study was designed to resolve this inconsistency. METHODS: We have measured the urinary excretion of a thromboxane metabolite, 11-dehydro-thromboxane B2, by a previously validated radioimmunoassay technique in 51 patients with acute cerebral ischemia who had experienced either a transient ischemic attack (14 patients) or an ischemic stroke (37 patients) and in 20 control patients with nonvascular neurological disorders. The median time between the onset of symptoms and urine sampling was 24 hours (range, from 2 hours to 8 days). RESULTS: The excretion rate of immunoreactive 11-dehydro-thromboxane B2 ranged between 39 and 478 pmol/mmol creatinine in patients with a transient ischemic attack and between 23 and 5,916 pmol/mmol creatinine in stroke patients, with 29% (p = 0.18) and 51% (p = 0.004) of the urine samples, respectively, exceeding the upper limit of the control samples (251 pmol/mmol creatinine [mean +/- 2 SD]) (p = 0.01). In stroke patients, metabolite excretion was not related to the type (cortical or "lacunar") or site of cerebral infarction. Low-dose aspirin (50 mg per day for 7 days) reduced the urinary excretion by approximately 85% in 11 consecutive stroke patients. CONCLUSIONS: We conclude that 1) episodes of enhanced thromboxane biosynthesis are detected infrequently in patients with a transient ischemic attack, 2) aspirin-suppressible episodes of increased thromboxane formation can be detected during the early phase of acute ischemic stroke, and 3) this finding may provide a rationale for testing the efficacy and safety of this drug in this setting.

Acute Disease↗
PubMed1993

Abnormally high thromboxane biosynthesis in homozygous homocystinuria. Evidence for platelet involvement and probucol-sensitive mechanism.

Homocystinuria due to homozygous cystathionine beta-synthase deficiency is an inborn error of metabolism characterized by a high incidence of thrombosis and premature atherosclerosis. We evaluated TXA2 biosynthesis in vivo and several in vitro tests of platelet function in 11 homocystinuric patients and 12 healthy controls. In vitro, patients' platelet aggregation was within control values as were TXB2 formation, fibrinogen binding, and ATP secretion in response to thrombin. In contrast, the urinary excretion of 11-dehydro-TXB2, a major enzymatic derivative of TXA2, was > 2 SD of controls in all patients (1,724 +/- 828 pg/mg creatinine, mean +/- SD, in patients vs. 345 +/- 136 in controls, P < 0.001). The administration to four patients of low-dose aspirin (50 mg/d for 1 wk) reduced metabolite excretion by > 80%. The recovery of 11-dehydro-TXB2 excretion over the 10 d that followed aspirin cessation occurred with a pattern consistent with the entry into the circulation of platelets with intact cyclooxygenase activity. Prolonged partial reduction in the abnormally high excretion of both 11-dehydro-TXB2 and 2,3-dinor-TXB2, was also observed in seven patients who ingested 500 mg daily for 3 wk of the antioxidant drug probucol. These results provide evidence for enhanced thromboxane biosynthesis in homocystinuria and for its partial dependence on probucol-sensitive mechanisms. Furthermore, the elevated TXA2 formation in homocystinuria is likely to reflect, at least in part, in vivo platelet activation.

Adolescent↗
PubMed1992

Evidence for a direct vasoconstrictor effect of big endothelin-1 in the rat kidney.

Inhibition of endothelin-1 (ET-1)-converting enzyme has been suggested as a strategy for blocking ET-1-mediated vasoconstriction. However, it is unclear whether its putative substrate, bigET-1, is an inactive precursor. Thus, we compared in the rat the effects of ET-1 and bigET-1 on renal vascular resistance (RVR) in vitro (isolated perfused kidney, n = 15) and in vivo (Doppler shift technique, n = 23) when injected i.v. or in the rat renal artery (i.a.), before and after metalloprotease inhibition with phosphoramidon (30 mg/kg i.v.). In vitro, the ET-1/bigET-1 potency ratio for the RVR increase was 175; in vivo (i.v.) it was approximately 7 (ED50: 99 and 692 pmol/kg, respectively; P < 0.01). Unlike that of ET-1, the bigET-1 effect started slowly (peak effect at 15 min). On i.a. injection, the ED50 of ET-1 was lower but that of big ET-1 was unchanged (ED50: 28 and 706 pmol/kg, respectively). Moreover, the effect of i.a. bigET-1 on RVR was biphasic, with a dose-related rapid increase followed by a slowly developing further rise. Phosphoramidon completely inhibited the hemodynamic effects of i.v. bigET-1, but abolished only the second phase of the response when given i.a. It also significantly enhanced the effect of ET-1. We conclude that in the rat: (1) bigET-1 may affect RVR by both a direct effect and through phosphoramidon-sensitive conversion to ET-1; (2) the direct vasoconstrictor effect of bigET-1 might be expressed during endothelin-converting enzyme inhibition; (3) metalloproteases are involved in ET-1 degradation.

Animals↗
PubMed1992

Increased thromboxane biosynthesis in patients with polycythemia vera: evidence for aspirin-suppressible platelet activation in vivo.

Increased thromboxane (TX) production and modified aspirin sensitivity has been detected in vitro in platelets isolated from patients with polycythemia vera. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo and its suppression by oral aspirin, we have investigated the urinary excretion of major enzymatic metabolites of TXB2 in 17 patients with polycythemia vera and 23 gender- and age-matched controls. Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. In addition, urinary immunoreactive leukotriene (LT) E4 was measured to explore the 5-lipoxygenase pathway of arachidonate metabolism. Polycythemic patients had significantly (P < .001) higher excretion rates of both 11-dehydro-TXB2 (1,033 +/- 1,050 v 117 +/- 45 pmol/mmol creatinine; mean +/- SD) and 2,3-dinor-TXB2 (725 +/- 676 v 82 +/- 43 pmol/mmol creatinine) than controls. In contrast, urinary LTE4 was not significantly different. Enhanced metabolite excretion did not correlate with the platelet count or with the hematocrit value, and was not related to the current treatment or to a clinical history of thrombotic complications. Platelet TX receptor studies did not show any significant changes in the binding characteristics of two different ligands. A platelet-selective regimen of aspirin therapy (50 mg/d for 7 to 14 days) was associated with greater than 80% suppression in metabolite excretion in nine patients. These results are consistent with abnormal stimuli operating in polycythemia vera to induce a selective enhancement in the platelet biosynthesis of TXA2 without changes in receptor binding. This in vivo abnormality in platelet biochemistry can be largely suppressed by low doses of aspirin.

Adult↗
PubMed1992

Thromboxane biosynthesis and metabolism in relation to cardiovascular risk factors.

Enhanced platelet biosynthesis of thromboxane A2 is associated with several cardiovascular risk factors, as a consequence of a direct effect on platelet biochemistry and/or some form of endothelial dysfunction. Moreover, episodic increases in thromboxane biosynthesis occur in acute coronary and cerebral ischemic syndromes. Thromboxane-dependent platelet activation represents an important mechanism that amplifies the consequences of acute vascular lesions as well as those of long-standing metabolic or hemodynamic disturbances, and results in increased risk of vascular occlusive events.

Animals↗
PubMed1992

Thromboxane synthesis and action within the kidney.

PGH2 and TxA2 exert their actions via tissue specific, receptor isoforms. PGH2/TxA2-dependent platelet aggregation and contraction of vascular and bronchial smooth muscle and of glomerular mesangial cells occur via receptors linked to activation of phospholipase C. Although PGH2/TxA2 appear to be of little importance in the maintenance of renal function under physiological circumstances, increased renal TxA2 biosynthesis has been documented in a variety of animal models of renal disease and in some clinical disorders (Table 2). The effects of this eicosanoid on renal tissues in vitro and of pharmacological manipulation of TxA2 synthesis and action in vivo suggest that such interventions will provide new drugs for the treatment of human kidney disease.

Animals↗
PubMed1992

Release of contracting autacoids by aortae of normal and atherosclerotic rabbits.

The aim of our study was to examine the release of various lipid and peptide contracting autacoids by aortae of normal and atherosclerotic rabbits. Leukotriene (LT) E4, an enzymatic derivative of LTC4, thromboxane (Tx) B2, and endothelin-1 (ET-1) were measured by radioimmunoassay techniques in aortic preparations of normal and cholesterol-fed rabbits. Intact aortae of normal rabbits incubated with the calcium ionophore A23187 for 1 h at 37 degrees C released LTE4 and TxB2 (22 +/- 3.5 and 14.8 +/- 2 pg/mg of tissue, respectively, mean +/- SEM, n = 33). Removal of aortic endothelium was associated with a significant reduction in LTE4 (44%) and TxB2 (58%) release. In aortic preparations from cholesterol-fed rabbits, the release of LTE4 was significantly enhanced (41 +/- 8 pg/mg of tissue, mean +/- SEM, n = 27) whereas TxB2 was not significantly altered. No detectable amounts of ET-1 were measured after 1 h of incubation. However, at 4 h, an endothelium-dependent release of ET-1 from normal aortae was demonstrated. In atherosclerotic aortae, ET-1 release was significantly higher than in controls (10 +/- 1.3 vs. 5 +/- 0.5 pg/cm2, mean +/- SEM, n = 16). We conclude that enhanced formation of vasoconstrictor autacoids may contribute to altered vasomotion of atherosclerotic blood vessels.

Animals↗
PubMed1992

Entry rate and metabolism of leukotriene C4 into vascular compartment in healthy subjects.

We measured the excretion of a major urinary metabolite of leukotriene (LT) C4, i.e., LTE4, during the infusion of exogenous LTC4 to enable estimation of the rate of entry of endogenous LTC4 into the bloodstream. Four healthy volunteers received 2-h intravenous infusions of vehicle alone and LTC4 at 0.063, 0.32, 1.6, and 2.9 pmol.kg-1.min-1 in random order. Urinary LTE4 was measured before, during, and up to 24 h after the infusions. The fractional elimination of LTE4 was independent of the rate of LTC4 infusion and averaged 4.3 +/- 0.9%. Calculation of the mean rate of entry of LTC4 into the circulation was found to be 0.06 pmol.kg-1.min-1. In addition, we characterized further metabolism of [14C]LTC4. The two major urinary metabolites were the omega- and beta-oxidation products (16-COOH-LTE4 and 14-COOH-LTE3), which accounted for 6-8% of the total infused amount of [14C]LTC4. We conclude that 1) LTC4 is produced at a low rate under physiological circumstances and is rapidly converted in the vasculature to LTE4, 2) changes in the urinary excretion of the latter may reliably reflect short-term changes in the rate of secretion of LTC4, and 3) measurement of the omega- and beta-oxidation products may reflect chronic changes in cysteinyl leukotriene biosynthesis.

Adult↗
PubMed1992

Increased thromboxane biosynthesis in type IIa hypercholesterolemia.

BACKGROUND: Increased platelet thromboxane (TX)A2 production has been described in type IIa hypercholesterolemia. To verify the relevance of these capacity-related measurements to the actual rate of TXA2 biosynthesis in vivo, we studied the urinary excretion of its major enzymatic metabolites in 46 patients with type IIa hypercholesterolemia and 20 age-matched controls. METHODS AND RESULTS: Urinary 11-dehydro-TXB2 and 2,3-dinor-TXB2 were measured by previously validated radioimmunoassays. The excretion rate of 11-dehydro-TXB2 was significantly (p less than 0.001) higher in patients (68.7 +/- 35.1 ng/hr, mean +/- SD) than in controls (22.4 +/- 9.4 ng/hr), with metabolite excretion greater than 2 SD of the normal mean in 74% of the patients. Urinary 11-dehydro-TXB2 was significantly (p less than 0.01) correlated with the threshold aggregating concentration of collagen (r = -0.641) and arachidonate (r = -0.734) and with agonist-induced platelet TXB2 production in vitro (r = 0.647 and 0.748, respectively). Moreover, a statistically significant correlation (r = 0.673, p less than 0.001, n = 66) was found between 11-dehydro-TXB2 excretion and total plasma cholesterol. The enzyme 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor simvastatin (20 mg/day for 6 months) significantly reduced cholesterol levels by 22-28% and urinary 11-dehydro-TXB2 excretion by 32-42% in 10 patients. However, the reduction in the latter did not correlate with the reduction in the former and may have resulted from a nonspecific effect of simvastatin. Moreover, selective inhibition of platelet cyclooxygenase activity by low-dose aspirin (50 mg/day for 7 days) was associated with cumulative inhibition of 11-dehydro-TXB2 excretion by approximately 70% in six patients. CONCLUSIONS: TXA2 biosynthesis is enhanced in the majority of patients with type IIa hypercholesterolemia; this is, at least in part, a consequence of abnormal cholesterol levels, as suggested by the correlation between the two. Low-dose aspirin can largely suppress increased metabolite excretion, thus suggesting that it reflects TXA2-dependent platelet activation in vivo.

Adult↗
PubMed1992

Human eicosanoid biosynthesis and metabolism.

The development of RIA techniques for the measurement of urinary eicosanoid metabolites has allowed characterization of their biosynthesis and metabolism in health and disease. PGI2, TXA2, and LTC4 share a very low rate of secretion into the human circulation and rapidly disappear from circulation because of extensive enzymatic degradation. Long-term changes as well as episodic increases in their biosynthesis can be detected in association with various disease states, as reflected by increased excretion of major enzymatic metabolites such as 2,3-dinor-6-keto-PGF1 alpha, 11-dehydro-TXB2, and LTE4. Application of the same investigative approach to other recently identified products of arachidonate metabolism (2) may provide further insight into the pathophysiologic significance of this complex mediator system.

Eicosanoids↗
PubMed1991

Inactivation of endothelin by polymorphonuclear leukocyte-derived lytic enzymes.

Cultured bovine aortic endothelial cells (BAEC) released endothelin-1 (ET-1) in the culture medium in a time-dependent fashion. Coincubation of fMLP-activated human polymorphonuclear leukocytes (PMN) with BAEC caused a fast (maximal activity was reached within 15 minutes) and cell number-dependent disappearance of ET-1 from the medium. This effect was direct to ET-1, because it was also present when PMN were incubated with the synthetic peptide in the absence of BAEC. PMN-dependent disappearance of ET-1 was associated with loss of constrictor activity on isolated rabbit aorta. PMN-released products were responsible for ET-1 degrading activity, because supernatants of activated PMN were equally effective as the intact cells. Resting PMN, in the same time frame, were uneffective. Eglin C, a potent blocker of PMN-derived elastase and cathepsin G, reversed the ET-1 inhibitory activity of fMLP-stimulated PMN and of their supernatant. Direct addition of elastase and cathepsin G to synthetic ET-1 destroyed its immunoreactivity and this effect was blocked by eglin C. High-performance liquid chromatography (HPLC) analysis supported the hypothesis that ET-1 degradation by PMN was due to enzymatic proteolysis. These data provide evidence that activated PMN are able to degrade ET-1 through the release of proteases. Because physiologic concentrations of PMN can destroy high amounts (up to 100 nmol/L) of ET-1 within a few minutes, we propose that this mechanism of ET-1 inactivation has biologic relevance.

Animals↗
PubMed1991

Heterologous in vivo processing of human preproendothelin 1 into bioactive peptides.

Endothelin (ET) is an extremely potent vasoconstrictor peptide of 21 amino acids, originally found in the supernatant of cultured vascular endothelial cells. To gain insights into its biosynthetic pathway, we expressed a synthetic RNA coding for the 212-amino acid precursor of human ET-1 (preproET-1) in Xenopus oocytes. Cell homogenates and oocyte incubation medium were tested by RIA using an anti-ET-1 serum. ET-1-like immunoreactivity was detected in oocytes injected with preproET-1 synthetic RNA but not in control oocytes and was much higher in medium than in cell homogenates. When preproET-1 was expressed in oocytes treated with monensin, a dramatic decrease in secretion of immunoreactive material was observed, indicating that secretion is mediated by the Golgi complex. ET-1-like immunoreactive material present in oocyte incubation medium was fractionated by reverse-phase HPLC into two main peaks, corresponding to the retention times of human big ET-1 and ET-1. Incubation medium of oocytes expressing the synthetic preproET-1 RNA elicited a characteristic vasoconstrictor response on rabbit vena cava, consistent with the biological activity that would be predicted from the amount of ET-1-like immunoreactivity measured. These results suggest that common pathways of ET maturation exist in widely different cells and that Xenopus oocytes may represent a useful tool in studying the cell biology of ET-1 synthesis.

Animals↗