Biomedical subjects

W W Lin

Publications and source records attributed to W W Lin.

At least 91 records · Page 5Linked to original sources

PubMed1992

Potentiation by Ca2+ ionophores and inhibition by extracellular KCl of endothelin-induced phosphoinositide turnover in C6 glioma cells.

Interactions between endothelin-1 (ET)-induced phosphoinositide (PI) hydrolysis and agents that increase Ca2+ influx (i.e. A23187 and ionomycin) or induce depolarization (i.e. KCl) were investigated using C6 glioma. A23187 dose-dependently potentiated ET (30 nM)- and ATP (100 microM)-induced [3H]inositol phosphate (IP) accumulation. This potentiation was associated with an increase in the maximal stimulation elicited by both ET and ATP but their EC50 values were unchanged. This effect of A23187 occurred at concentrations that did not affect basal PI turnover; i.e. 10 nM-3 microM. Ionomycin within the range of 1 nM-1 microM also significantly enhanced ET-induced PI breakdown and this effect was associated with an increase of [Ca2+]i. KCl in a concentration-dependent manner (14.7-54.7 mM) markedly inhibited PI breakdown elicited by ET and ATP, but had much less inhibition on basal activity and no effect on A23187- and ionomycin-induced responses. In parallel, KCl added before or after ET, sharply attenuated the increase of ET-induced [Ca2+]i but did not affect basal level or ionomycin-induced [Ca2+]i response. Neither the potentiation by A23187 nor the inhibition by KCl of ET-induced PI turnover was observed in cultured cerebellar astrocytes. Our results suggest that the cell type-specific regulation by Ca2+ ionophores and KCl on ET-induced PI metabolism is closely related to perturbation of [Ca2+]i.

Adenosine Diphosphate↗

PubMed1992

Differences in left ventricular structural and functional changes between pheochromocytoma and essential hypertension. Role of elevated circulating catecholamines.

Experimental findings suggest that catecholamines increase protein synthesis and play a role in cardiac hypertrophy. We hypothesize that elevated circulating plasma catecholamines in pheochromocytoma influence cardiac structural and functional remodeling. We compared 15 patients with surgically proven pheochromocytoma and 15 with untreated essential hypertension; we matched the patients for age, sex, body surface area, and blood pressure (BP) levels. Left ventricular hypertrophy (LVH) was identified by M-mode echocardiography in six patients with pheochromocytoma and in four with essential hypertension. Among both groups there were no differences in cardiac structure, no correlation between left ventricular mass and BP, no significant differences in mitral E-F slope, no correlation between either plasma norepinephrine or plasma epinephrine levels, and no differences in the left ventricular structural indices measured. In the pheochromocytoma group, left ventricular end systolic stress and end systolic diameter were significantly lower and left ventricular percent fractional shortening was higher. Plasma norepinephrine levels were higher in the pheochromocytoma group, but did not differ among patients of that group with and without LVH. We conclude that in both pheochromocytoma and essential hypertension, only a subset of patients develop evidence of LVH, and that in pheochromocytoma, the elevation of circulating plasma catecholamines is not necessarily associated with LVH. These results indicate that factors other than catecholamines and BP determine the development of LVH in pheochromocytoma.

Adolescent↗

PubMed1992

Influences of castration and testosterone on spring to summer changes in release of luteinizing-hormone-releasing hormone in rabbits.

Push-pull cannulae were implanted toward the tuberal region of the hypothalamus in ten intact New Zealand male rabbits. In the first experiment, rabbits were perfused at different times after castration: 5-10 days (n = 10), 22-31 days (n = 9) and 50-64 days (n = 8). The release, mean amplitude and mean frequency of luteinizing-hormone-releasing hormone (LHRH) signals from 37 perfusions in ten animals were analysed in intact rabbits and at different times after castration. No significant changes in release of LHRH and in amplitude were observed, but the frequency was significantly higher 22-31 days after castration than in intact rabbits (intact: 0.86 +/- 0.12; castrated: 1.20 +/- 0.13 pulses h-1, P < 0.035; n = 9). In Expt 2, testosterone and placebo Silastic capsules were implanted in the castrated rabbits. Perfusions were performed in the following four periods, defined by season and time after testosterone and placebo implants: (i) spring; before implants, (ii) late spring; 0-2 weeks after implants, (iii) summer solstice; 2-4 weeks after implants and (iv) summer; 4-6 weeks after implants. Castrated rabbits were perfused during spring; castrated rabbits with testosterone capsule implants were perfused during late spring, around summer solstice and in summer and castrated rabbits with placebo implants were perfused during periods (iii) and (iv). Castrated animals with placebo implants showed no significant changes in mean LHRH release and amplitude, although the frequency was significantly higher around the summer solstice period than in castrated rabbits perfused in the spring. In castrated rabbits with testosterone implants LHRH release was significantly higher in late spring than around the summer solstice and in the summer. In addition, the concentrations of LHRH in late spring were significantly higher than those of intact and castrated animals. In contrast, mean LHRH amplitude and frequency did not change. Mean amount of LHRH released and amplitude in castrated rabbits with testosterone implants were significantly lower around the summer solstice than in late spring or summer and compared with intact animals around summer solstice and in castrated rabbits in early spring. These data demonstrate that there were no significant changes in the mean amplitude and release of LHRH after castration from 5 and up to 64 days in rabbits with hypothalamic push-pull cannulae, in contrast to the well established dramatic effect of castration on gonadotrophin concentrations. However, there was a small, but significant, increase in the mean frequency of LHRH pulses 22-31 days after castration compared with values from intact rabbits.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗

PubMed1992

Pharmacological characterization of endothelin-stimulated phosphoinositide breakdown and cytosolic free Ca2+ rise in rat C6 glioma cells.

Because increasing evidence indicates that glial cells are a target of endothelin, we have characterized endothelin-induced phosphoinositide (PI) turnover and Ca2+ homeostasis in C6 glioma cells. Endothelin-1 (ET) increased formation of 3H-inositol phosphate (IP) from PI and elicited an increase in cytosolic free Ca2+ ([Ca2+]i) in rat C6 glioma. In the presence of Li+, the increase in 3H-inositol trisphosphate formation was rapid, reaching its peak at 5 min after stimulation. ET also elicited a rapid and sustained increase in [Ca2+]i in a dose-dependent manner (1-100 nM). The rank orders of efficacy for ET-related peptides in increasing [Ca2+]i were ET = ET-2 greater than sarafotoxin greater than ET-3. Both ET-mediated stimulation of IP formation and [Ca2+]i increase were largely inhibited in the absence of external Ca2+ but unaffected by the depletion of external Na+ and the presence of dihydropyridine derivatives or verapamil. Inorganic Ca2+ channel blockers Cd2+, La3+, and Mn2+ at 1 mM inhibited both responses induced by ET. Cross-desensitization and nonadditivity were observed for both events among ET-related peptides tested, but not between ET and ATP. Pretreatment of cells with pertussis toxin (PTX) attenuated the PI response to ET, but had no effect on ET-elicited [Ca2+]i increase. ET-induced Ca2+ mobilization (measured in Ca(2+)-free medium) was only transient and was inhibited by 8-(N,N-diethylamino)octyl-3,4,5-trimethoxybenzoate. Moreover, the intracellular Ca2+ pools mobilized by ET and ATP appeared to overlap, as indicated by their partial heterologous desensitization.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenosine Triphosphate↗

PubMed1992

Pericardiocentesis: a 20 patients study.

Emergency pericardiocentesis, guided by a two-dimensional echocardiography, was performed on twenty patients with symptomatic pericardial effusion of various types and causes. There were fourteen men and six women. The underlying causes were: primary lung cancer (6 cases), metastatic cardiac tumors (3 cases), tuberculosis (4 cases), complicated interventional procedures with cardiac chamber or vessel perforations (2 cases), dissecting aortic aneurysm (1 case), systemic lupus erythematous (1 case), idiopathic pericarditis (1 case), bacterial pericarditis (1 case), and myxedema heart disease (1 case). Seventeen cases were performed through the left xipho-sternal approach and 3 cases through the apical approach. None of the patients died as a result of these procedures. A two-dimensional echocardiogram is useful in diagnosing cardiac tamponade as well as in guiding pericardiocentesis, and obtaines highly positive results (20/20). The positive rate of pericardial fluid cytology for malignant cells was 89% (8/9), however, pericardial fluid cultures or direct smear for tuberculosis were negative (0/4). In cancer patients, the mean survival time following pericardiocentesis was 4.2 months (range, 1-7.8 months). We concluded that neoplastic involvement of the pericardium is the most frequent cause of symptomatic pericardial effusion. Pericardiocentesis assisted by a two-dimensional echocardiogram is safe and easy. In addition, pericarditis caused by TB is still significant and must be considered in every case in our nation.

Adult↗

PubMed1992

Fibromuscular dysplasia of the brachial artery: a case report and review of the literature.

Fibromuscular dysplasia is a nonatherosclerotic, noninflammatory vascular disease that involves primarily medium-sized and small arteries. Fibromuscular dysplasia is characterized by medical fibrosis with or without smooth muscle cell hyperplasia and may produce luminal impingement with severe turbulence. Secondary aneurysmal deformity with or without thrombosis may also contribute to the obstruction. Fibromuscular dysplasia most commonly involves the renal and carotid arteries, with upper-extremity disease rarely reported. This case report describes a patient with digital embolization from brachial artery fibromuscular dysplasia. Angiography demonstrated significant narrowing and irregularity with a characteristic "string-of-beads" appearance of the right midbrachial artery. The abnormal segment was resected and reconstructed with a reversed saphenous vein graft. Histologic studies revealed disruption of the internal elastic lamina and disorientation of the hyperplastic medial smooth muscle cells characteristic of fibromuscular dysplasia.

Aged↗

PubMed1991

In vivo models for the study of gonadotropin and LHRH secretion.

The objective of this paper is to describe recent data from my laboratory dealing with the in vivo control of LHRH secretion in male rabbits and rats using the technique of push-pull perfusion (PPP) that allows repetitive determinations of this neuropeptide in quasi-normal physiological conditions. In addition, we have applied this method to simultaneously measure LHRH and LH in freely behaving male rats bearing a push-pull cannula (PPC) in the anterior pituitary. A description of the validation of this technique and its potential use will be discussed as well as data indicating that castration in the male rat induces a significant increase in the LHRH and LH signals; however, following testosterone treatment, in spite of a clear return of LH output to intact levels, even higher levels of LHRH reaching the anterior pituitary were detected. Curiously, in the rabbit no changes in LHRH release were noticed with castration, but following testosterone treatment, a transient but robust 5-8-fold increase in LHRH release was noticed. In short, these studies have demonstrated the existence of apparently opposite rather than similar responses in the testicular control of the hypothalamic-hypophysial axis of the male rat as compared with those of the male rabbit.

Animals↗

PubMed1991

Effect of mating behavior on luteinizing hormone-releasing hormone release in female rabbits as monitored with push-pull cannulae.

To examine the effect of mating behavior on luteinizing hormone-releasing hormone (LHRH) release, intact New Zealand female rabbits were implanted with push-pull cannulae (PPC) aimed at the tuberal region of the hypothalamus and perfused with modified Krebs-Ringer phosphate medium at 11-13 microliters/min. In the mating experiments, does (n = 10) were initially perfused for a control period of 60-170 min followed by a mating period (100-160 min) which included the introduction of the male rabbit for an average time period of 30 min. Two groups of LHRH release patterns were observed: positive and negative responders. In the positive LHRH responders (n = 5), a clear rapid increase in LHRH release following mounting by the male occurred with a significant increase in the mean LHRH release (1.83 +/- 0.33 to 3.27 +/- 0.80 pg/10 min, p less than 0.040), in the mean LHRH amplitude (1.97 +/- 0.46 to 4.33 +/- 1.29 pg, p less than 0.022) and in the amplitude of the largest LHRH pulse (2.13 +/- 0.43 to 7.58 +/- 3.65 pg, p less than 0.022). In the negative LHRH responders (n = 5), no changes in LHRH release were detected although all rabbits ovulated, with some becoming pregnant. It appears from histological analysis that the difference between these two patterns of responses following mating are due to different cannula placements. In the positive responders, the tip of the PPC was localized in the tuberal region whereas in the negative responders, the placements were more dorsal and, in some cases, anterior.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1991

Seasonal changes in the in-vivo activity of the luteinizing hormone-releasing hormone (LHRH) neural apparatus of male rabbits monitored with push-pull cannulae.

Intact sexually mature New Zealand White male rabbits, raised under natural lighting and temperature conditions, were isolated and housed in air-conditioned quarters, in a 12-h light:12-h dark cycle. Push-pull cannulae were implanted towards the tuberal region of the hypothalamus, and animals were perfused with modified Krebs'-Ringer phosphate medium for an average period of 4 h. Most rabbits were repetitively perfused over an average period of 3.7 months. Perfusions were grouped into seasonal periods of about 40 or 80 days through the entire 1-year cycle: (A) 23 November to 31 December (winter solstice period: N = 6), (B) 1 January to 23 March (winter: N = 10), (C) 24 March to 13 June (spring: N = 9), (D) 14 June to 23 July (summer solstice period: N = 23), (E) 24 July to 13 October (late summer-early fall: N = 7) and (F) 14 October to 22 November (fall: N = 4). Maximal and minimal values of mean release, mean amplitude and mean frequency from every animal in each block were obtained. In the summer solstice group (D), maximal mean (+/- s.e.) LHRH release levels were significantly greater (14.42 +/- 6.62 pg/10 min) than for all groups (A, 0.76 +/- 0.27; B, 1.59 +/- 0.39; C, 1.34 +/- 0.22; E, 1.33 +/- 0.33; and F, 1.18 +/- 0.11) while during the winter solstice period (A), minimal mean LHRH release levels (0.48 +/- 0.04 pg/10 min) were significantly lower than in all other groups (B, 1.43 +/- 0.41; C, 0.96 +/- 0.11; D, 7.25 +/- 4.12; E, 1.18 +/- 0.37; and F, 1.18 +/- 0.11). Maximal values were highest during the summer solstice period while the minimal values were lowest during the winter solstice period. The amplitude and frequency of the LHRH pulses showed changes similar to those observed with the mean LHRH release. For 1 year, an estimated left testis weight was measured in 4-7 rabbits every 2-5 weeks. The percentage estimated testis weight peaked in early August and reached minimal levels during the winter months. These data demonstrate that the rabbit LHRH neural apparatus is very sensitive to seasonal influences although animals remained in a fixed photoperiod during the entire duration of the experiment.

Animals↗

PubMed1991

Endothelin- and sarafotoxin-induced phosphoinositide hydrolysis in cultured cerebellar granule cells: biochemical and pharmacological characterization.

Endothelin (ET)-1, -2, -3, big ET-1 and sarafotoxin S6b (S6b) dose-dependently increased phosphoinositide (PI) hydrolysis by 6- to 10-fold in cultured cerebellar granule cells prelabeled with [3H] myoinositol. The PI response elicited by ET-1 was dependent on the presence of extracellular Ca++, but was not reduced by organic (nisoldipine, nimodipine) or inorganic (Co++, Mn++) calcium channel blockers. Pretreatment of granule cells with tetrodotoxin or amiloride failed to affect the response to ET-1. Extracellular sodium depletion resulted in a marked increase in basal PI turnover; however, the net increase of PI turnover induced by ET-1 was unchanged. ET-induced PI breakdown could be partially inhibited by short or long term treatment with phorbol dibutyrate but was unaffected by pertussis toxin. ET- and S6b-induced PI turnover were dependent on the culturing time of granule cells, with the maximal response in a 4-day culture. The ET- and S6b-induced PI turnover appeared to be additive to that induced by carbachol, histamine, norepinephrine, serotonin, glutamate and maitotoxin. However, the responses induced by ET and S6b were nonadditive. Prestimulation of cells with ET or S6b for 30 sec to 24 hr resulted in dramatic loss of the ability of ET and S6b to stimulate PI hydrolysis, without affecting subsequent responsiveness induced by other stimuli, indicating homologous desensitization for ET- and S6b-induced responses. Moreover, our results further support the notion that ET and S6b act on the same population of receptors in cerebellar granule cells.

Animals↗

PubMed1991

Endothelin-induced activation of phosphoinositide turnover, calcium mobilization, and transmitter release in cultured neurons and neurally related cell types.

Endothelin (ET)-related peptides robustly stimulated [3H]-inositol phosphate (IP) formation in cultured cerebellar granule cells, astrocytes, and C6 glioma cells. Their agonist selectivities were ET-1 = ET-2 greater than or equal to sarafotoxin S6b greater than ET-3 greater than big ET-1 for granule cells and ET-1 greater than or equal to ET-2 greater than or equal to S6b greater than big ET-1 greater than ET-3 for cerebellar astrocytes and C6 glioma cells. These effects were Ca(2+)-dependent but insensitive to antagonists of L-type Ca2+ channels and the Na+/Ca2+ antiporter. Pretreatment of cells with ET-1 or S6b induced homologous desensitization of phosphoinositide (PI) response mediated by ET receptors. Long-term pertussis toxin (PTX) treatment attenuated the phosphoinositide (PI) response in astrocytes and glioma but not in granule cells. ET-1 and its related peptides increased [Ca2+]i in C6 glioma by two distinct pathways: IP3-induced Ca2+ mobilization or receptor-operated Ca2+ influx. La3+, Mn2+, and Cd2+ inhibited the Ca2+ influx and sustained PI turnover, while Ca2+ mobilization was attenuated by phorbol ester and TMB-8. ET-induced Ca2+ influx was essential for the sustained [Ca2+]i increase and PI turnover. Homologous desensitization of [Ca2+]i increase was also noted. In cerebellar granule cells, ET evoked the release of [3H]D-aspartate from these neurons. This action appears to be dependent on PI hydrolysis and [Ca2+]i increase and modulated by protein kinase C.

Animals↗

PubMed1990

Comparative studies of phosphoinositide hydrolysis induced by endothelin-related peptides in cultured cerebellar astrocytes, C6-glioma and cerebellar granule cells.

Effects of endothelin (ET) homologues (ET-1, 2, 3 and sarafotoxin S6b) and its precursor (big ET-1) on phosphoinositide (PI) turnover were compared in neurally-related cell cultures. All ET-related peptides induced a robust increase of PI turnover in cerebellar astrocytes, C6-glioma and cerebellar granule cells. The rank order of potency in stimulating PI turnover was ET-1 = ET-2 greater than or equal to S6b greater than ET-3 greater than big ET-1 for granule cell neurons, while it was ET-1 greater than or equal to ET-2 greater than or equal to S6b greater than big ET-1 greater than ET-3 for astrocytes and C6-glioma cells. Short-term pretreatment with phorbol dibutyrate (PDBu) attenuated the ET-1-induced PI response in all three types of cultures. However, long-term pretreatment with PDBu attenuated the response in granule cells and C6-gliomas, but enhanced responses to ET and ATP in astrocytes. Long-term exposure of cells to pertussis toxin (PTX) attenuated the PI response to ET in astrocytes and C6-gliomas, but not in granule cells. Thus, phospholipase C-coupled ET receptors are expressed in both neurons and glial cells, but they differ considerably in their pharmacological selectivity and signal transduction mechanisms in stimulating PI hydrolysis.

Animals↗

PubMed1990

Endothelin-1 stimulates the release of preloaded [3H]D-aspartate from cultured cerebellar granule cells.

We have recently reported that endothelin-1 (ET) induces phosphoinositide hydrolysis in primary cultures of rat cerebellar granule cells. Here we found that ET in a dose-dependent manner (1-30 nM) stimulated the release of preloaded [3H]D-aspartate from granule cells. The ET-induced aspartate release was completely blocked in the absence of extracellular Ca2+, but was unaffected by 1 mM Co2+ or 1 microM dihydropyridine derivatives (nisoldipine and nimodipine). At higher concentration (10 microM) of nisoldipine and nimodipine, the release was partially inhibited. Short-term pretreatment of cells with phorbol 12,13-dibutyrate (PDBu) potentiated the ET-induced aspartate release, while long-term pretreatment with PDBu attenuated the release. Long-term exposure of cells to pertussis toxin (PTX), on the other hand, potentiated the ET-induced effects. Our results suggest that ET has a neuromodulatory function in the central nervous system.

Animals↗

PubMed1990

Biphasic effects of endothelin in the guinea-pig ileum.

The intestinal effects of porcine endothelin (ET-1), a potent endothelium-derived vasoconstrictor, were studied on the guinea-pig isolated ileum. ET-1 (3 x 10(-10)-3 x 10(-7) M) caused biphasic responses on spontaneous smooth muscle tone, an initial relaxation followed by a late contraction. The contractile response was elicited in a concentration-dependent manner. Both the relaxing and contractile phases were not affected by pretreatment with tetrodotoxin, phentolamine, tolazoline, propranolol, guanethidine, 8-phenyl-theophylline, naloxone, methylsergide, [D-Pro4,D-Try7,9]SP-(4-11), diphenylhydralamine and indomethacin. Atropine (3 x 10(-7) M) also had no effect on the ET-1-induced contraction. The ET-1-induced contraction, however, was markedly inhibited by verapamil (greater than 10(-8) M) and H-7 (3 x 10(-5) M). These results suggest that, in intestinal smooth muscle, ET-1-induced contraction can be attributed to the direct effect on muscle and appears to be mediated by increased Ca2+ influx through voltage-dependent Ca2+ channels as well as protein kinase C activation. On the other hand, ET-1-induced relaxation is due neither to the indirectly evoked release of inhibitory neurotransmitters nor to the direct activation of adrenoceptors, and purine and opiate receptors. The exact mechanism responsible for ET-1-induced relaxation needs to be further studied.

Animals↗

PubMed1990

Detection of prosthetic mitral valve leak: a comparative study using transesophageal echocardiography, transthoracic echocardiography, and auscultation.

Paravalvular leakage is a major complication of prosthetic valve dysfunction. Sixty-one subjects with valvular heart disease who had received prosthetic mitral valve replacement 5 months to 5 years before (43 received a porcine prosthesis and 18 received Bjork-Shiley valve prostheses) were evaluated for this complication. Careful auscultation was performed by two experienced cardiologists followed by transthoracic and transesophageal echocardiography. Physiologic leaks were detected in all Bjork-Shiley valves, but in only 30% of porcine valves using transesophageal echocardiography. These regurgitant jets were flame-like, with mean low velocities of 50 +/- 12.3 cm/sec and 48 +/- 18.2 cm/sec in the two types of valves. Neither transthoracic echocardiography nor auscultation could detect physiological regurgitant jets. Ten cases with paravalvular leak were detected by transesophageal echocardiography and subsequently demonstrated by left ventriculography (7 porcine, 3 Bjork-Shiley valves). Pathologic regurgitant jets were seen as high-velocity, systolic-retrograde turbulent flow across the prosthesis. However, only 6 cases of prosthetic valve dysfunction were detected by transthoracic echocardiography, 4 cases of mild paravalvular leakage went undetected. Thirteen of the 61 subjects had an apical systolic murmur and suspected prosthetic valve leakage; in 10 of the 13 cases the findings corresponded to those obtained by transesophageal echocardiography. In 3 cases of double valve replacement with Bjork-Shiley valves the magnitude of the leakage was overestimated by auscultation.

Adult↗

PubMed1990

Cardiovascular effects of two disulfide analogues of sarafotoxin S6b.

Sarafotoxin S6b (STX-b), a peptide toxin isolated from the venom of the Israeli burrowing asp, Atractaspis engaddensis, consists of 21 amino acid residues with four cysteines at positions 1,3,11 and 15. In the present study, we compared the cardiovascular effects of two synthetic STX-b analogues with different disulfide bridge locations, i.e. STX-b type A (1-15, 3-11) and STX-b type B (1-11, 3-15). At doses of 0.3-3 nmoles/kg (i.v.), type A produced a sustained pressor effect with transient increase in pulse pressure. However, at 5 nmoles/kg, it produced a transient increase followed by decrease in blood pressure, heart rate and respiratory rate within 30 sec and 12 out of 13 mice died within 10 min. Various kinds of ECG changes, suggestive of myocardial ischemia and hyperkalemia, were observed. Type A also caused a significant increase in the plasma levels of K+, lactate dehydrogenase, creatine phosphokinase, inorganic phosphate and glucose. By contrast, type B did not kill any mouse at doses up to 50 nmoles/kg. In the rat aorta, type A caused a potent vasoconstriction which was dependent on extracellular Ca2+ and was partially inhibited by verapamil and H-7, a protein kinase C inhibitor. In the rat Langendorff heart preparation, type A produced coronary vasospasm with potency about 100 times higher than that of type B. A similar potency ratio was observed for the positive inotropic effect in rat atria. These results indicate that the location of disulfide bridges in sarafotoxin S6b markedly influences the pharmacological potency and the natural sarafotoxin S6b should be type A with the disulfide bridge locations at positions 1-15 and 3-11.

1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine↗

PubMed1990

Maitotoxin induces phosphoinositide turnover and modulates glutamatergic and muscarinic cholinergic receptor function in cultured cerebellar neurons.

Maitotoxin (MTX) stimulated inositol phosphate (IP) formation in primary cultures of rat cerebellar granule cells. MTX-induced IP production was dependent on extracellular Ca2+ but independent of extracellular Na+. The stimulation of IP formation elicited by MTX was unaffected by pretreatment of cells with phorbol dibutyrate, pertussis toxin, and a variety of Ca2+ entry blockers, such as nimodipine, nisoldipine, Co2+, and Mn2+. The presence of MTX markedly attenuated IP production induced by carbachol and glutamate, with no apparent effect on the responses to norepinephrine (NE), histamine, 5-hydroxytryptamine (5-HT), and endothelin-1. The inhibition of the carbachol- and glutamate-induced responses by MTX was dose dependent with IC50 values of 1.2 and 0.5 ng/ml, respectively. Pretreatment of cells with a lower concentration of MTX (0.3 ng/ml) also attenuated carbachol- and glutamate-induced IP formation, in a time-dependent manner, with a decrease observed after 30 min prestimulation, but failed to affect NE-, histamine-, 5-HT-, endothelin-1, and sarafotoxin S6b-induced responses. Thus, MTX elicited a marked Ca2(+)-dependent phosphoinositide (PI) turnover in cerebellar granule cells and selectively inhibited carbachol- and glutamate-induced PI hydrolysis. Possible mechanisms underlying these selective modulations are discussed.

Animals↗

PubMed1990

A reevaluation of the hemodynamics of pheochromocytoma.

We examined the hemodynamic features of 24 untreated patients with surgically proven pheochromocytoma during steady-state periods and compared them with 24 untreated essential hypertensive patients individually matched for sex, age, body surface area, and arterial blood pressure. We found that, despite having 10-fold higher levels of circulating catecholamines, pheochromocytoma patients have hemodynamic characteristics similar to patients with essential hypertension and that, in individual patients, the ratio of circulating norepinephrine to epinephrine had no relation to the hemodynamic profile. In both groups, increased total peripheral resistance is primarily responsible for maintenance of hypertension. These results suggest that, unlike the acute administration of catecholamines, long-term exposure to high levels of circulating catecholamines does not produce hemodynamic responses characteristic of this group of compounds. This might be due in part to desensitization of the cardiovascular system to catecholamines and might explain the clinical observation that some patients can be completely asymptomatic despite harboring an actively catecholamine-secreting pheochromocytoma.

Adrenal Gland Neoplasms↗