Presence Of Norepinephrine Research Articles

Effects of Ca++-antagonists on systemic capacitance vessels and venous return curves of dogs--a study with mean circulatory pressure.

We measured mean circulatory pressure (MCP) in anesthetized, open-chest dogs before and after intravenous administration of Ca++-antagonists to estimate the effects on systemic capacitance vessels and on venous return (VR) curves both with and without continuous intravenous infusion of norepinephrine (NE). Diltiazem (300 micrograms/kg) decreased total peripheral resistance (TPR) and MCP significantly. Nifedipine (5 micrograms/kg), nicardipine (30 micrograms/kg) and verapamil (200 micrograms/kg) decreased TPR significantly without any change in MCP in the absence of NE, but with the exception of verapamil, they decreased MCP in the presence of NE. This indicates that diltiazem relaxed the systemic capacitance vessels, and nifedipine and nicardipine significantly decreased the tone of the systemic capacitance vessels that had been previously elevated by NE, but this action was very slight with verapamil. These Ca++-antagonists rotated VR curves clockwise, decreased resistance to VR (RVR) and increased VR both in the presence and absence of NE. It was suggested that the decrease in the RVR would be at least partially responsible for the increase in the VR.

Characteristics of contractile response of isolated portal veins from chronic portal hypertensive rats under altered levels of external K+, Ca2+, and norepinephrine concentrations: a comparison with normal Wistar rats.

We studied contractile properties of portal veins isolated from chronic portal hypertensive rats (PHR) resulting from liver cirrhosis, a model obtained by repeated subcutaneous injections of CCl4 (2 mg/kg) twice weekly for over 45 weeks. Portal venous pressure in vivo was significantly higher in PHR (167.0 +/- 38.7 mmH2O) than in the control normal Wistar rats (NWR) (102.0 +/- 25.5 mmH2O). A pair of portal veins from PHR and NWR were mounted longitudinally in an organ bath and perfused with Tyrode's solution with different K+, Ca2+, and norepinephrine concentrations. The isometric tension was measured by a strain-gauge. Under control conditions, spontaneous phasic contractile force, corrected by cross-sectional area, was greater, and the frequency was lower in PHR than in NWR preparations. The averaged peak contractile force measured at different [K]o (5.4-86.4 mM) was also greater in PHR than in NWR. Force of the tonic contraction measured at different [Ca]o (0.45-5.4 mM), under conditions of 86.4 mM [K]o was significantly larger in PHR than in NWR preparations. However, the Ca2+ sensitivity of both preparations was the same. D-600 (greater than or equal to 0.1 microM) inhibited the tonic contraction in both preparations with an identical sensitivity to the drug. In the presence of norepinephrine (10 microM), the Ca2+ sensitivity of the tonic contraction increased both in PHR and NWR preparations. The increase was more pronounced in PHR and was completely reversed in the presence of the alpha 1-adrenoceptor blocker, prazosin (0.1 microM). The alpha 1-adrenoceptor sensitivity to norepinephrine was not altered in PHR preparations. The rate of Ca2+ release and uptake of intracellular Ca2+ seemed identical in both preparations. Thus, in the absence of norepinephrine, the phasic and tonic contractile forces of portal veins from PHR are larger than that of NWR, probably due to increased membrane Ca2+ permeability. The PHR preparations have a higher affinity for external Ca2+ in the presence of norepinephrine, an additional factor contributing to elevation of portal blood pressure in the presence of chronic liver cirrhosis.

Renal Hemodynamic Effects of Calcium Antagonists

Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment glomerular filtration rate but produce only a modest improvement in renal perfusion. This preferential augmentation of glomerular filtration rate may be attributable to a selective vasodilation of preglomerular vessels. Although the clinical implications of such observations are not yet clear, preliminary studies in experimental animal models indicate that calcium antagonists may exert salutary effects on renal function in clinical settings that are characterized by impaired renal hemodynamics. The possible benefits of calcium antagonists in ameliorating the development of renal dysfunction in patients in whom there is increased risk for the development of acute renal insufficiency remain to be evaluated.

Ryanodine in mammalian heart ventricular muscle: indication for the induction of calcium leakage from the sarcoplasmic reticulum

Ryanodine at nanomolar concentrations suppressed the earlier of two contraction components which can be produced in guinea-pig papillary muscles, in the presence of noradrenaline (3 μM) at a low contraction frequency (0.2 Hz). However, test contractions elicited shortly after a steady contraction showed an unimpaired early contraction component. This component declined with increases in the interval preceding the test contraction at a rate depending on the ryanodine concentration (the apparent first-order rate constant 0.07 s −1 of the spontaneous decline was doubled by about 0.2 nM and was increased to 1.3 s −1 by 10 nM ryanodine). The effect of ryanodine resembled that of a potassium-induced depolarization with the exception that it was not antagonized by an increase in the extracellular magnesium concentration. It is concluded that ryanodine enhances the leakage of stored calcium in mammalian heart ventricular muscle, probably by a direct influence on the calcium release channels of the junctional sarcoplasmic reticulum of the heart muscle cell.

Enhancement of the response of hen granulosa cells to LH with norepinephrine in vitro

1. 1. The effect of norepinephrine (NE) on progesterone production in hen granulosa cells was examined. After 4 days of the culture, the progesterone production was stimulated by chicken LH but not by NE during a 4hr incubation. 2. 2. The LH-stimulation progesterone production was not affected by the presence of NE when given together with LH, but was significantly increased when the cells were precultured with NE for 2 days. 3. 3. The effect of NE was inhibited by phentolamine, but not by propranolol. 4. 4. The results indicate that NE may enhance the responsiveness of the hen granulosa cell to LH through α-adrenergic receptors.

Intracellularly recorded responses to tilt and efferent input of statocyst sensory cells in the pulmonate snail Lymnaea stagnalis

1. 1. The morphology of the statocyst sensory cells in Lymnaea was investigated by backfiling the statocyst nerve with HRP. Two types of cells were found: small and large. 2. 2. Responses of statocyst sensory cells were recorded intracellularly upon tilts of different amplitudes. The stimulus response plots showed that there were two types of cells which differed in sensitivity. There was a linear relationship between stimulus and firing rate, stimulus and amplitude of the receptor potential and between receptor potential and firing rate. 3. 3. The statocyst sensory cells receive efferent input from mechanoreceptors in the skin from the eyes and from oxygen-sensitive detectors in the mantle-lung area. This input is probably of synaptic origin. 4. 4. Aminergic drugs applied to the preparation produced hyperpolarizations in the statocyst sensory cells resembling the responses upon exposure of the mantle-lung area to air with low oxygen content. Indications were obtained that noradrenergic β-receptors are involved in the aminergic responses. 5. 5. In the presence of noradrenalin, the responses of the statocyst sensory cells upon tilt decreased.

Stimulation of melatonin synthesis in ovine pineals in vitro.

Static and superfused pineal slices (750 micron) have been used to study the control of melatonin synthesis by ovine pineals. Static incubates show a time-dependent accumulation of melatonin in the medium; this is significantly increased by stimulation with norepinephrine (NE) (10(-5) M), reaching 300% above control levels after 4 h. Perifused pineal slices show a rapid rise in melatonin release within 12-18 min in response to NE stimulation. This reaches a 3.5-4.5-fold increase in melatonin released within 30 min. Withdrawal of NE is associated with a rapid return to prestimulated levels within 12-18 min. These time-course characteristics compare favorably to those changes seen in vivo. The formation of [14C]melatonin from [14C]-tryptophan shows a linear increase with time. In the presence of NE (10(-5) M), the rate of synthesis is increased, albeit after an initial time lag of at least 30 min. The latter may reflect an N-acetyltransferase-independent mechanism of synthesis and release. In static incubations, propranolol (10(-5) M) inhibited NE-induced melatonin production by about 60%, but prazosin (10(-5) M) had no effect. As dibutyryl cyclic AMP (10(-3) M) stimulated melatonin production, it is concluded that beta-receptors are of primary importance to the control of melatonin production, as in the rat. The role of alpha 1-receptors is less clear, but the stimulatory action of phorbol 12-myristate 13-acetate on melatonin release implicates a receptor linked to phosphatidylinositol turnover.

Arachidonate incorporation into phospholipids in rat brain: A comparison between slice and membrane preparation

The incorporation of [(3)H]arachidonic acid ([(3)H]AA) into cerebral phospholipids was studied in slices and membranes of rat brain cortex. Effects of preincubation, different washing procedures with or without bovine serum albumin, or incubation in the presence of neurotransmitters were investigated. Over 60% of the phospholipid-bound [(3)H]arachidonic acid was recovered in phosphatidylinositol in both slice and membrane preparations. Preincubation or addition of bovine serum albumin resulted in slower incorporation of the isotope to membrane as well as to slice phospholipids, but removal of the added serum albumin enhanced the incorporation in the membrane preparation. Preincubation of slices in the presence of norepinephrine (1 mM) or serotonin (1 or 2.5 mM) resulted in a marked increase of [(3)H]arachidonate incorporation into phosphatidylinositol concomitant with decreased incorporation into other phosopholipids. Analysis of [(3)H]arachidonate incorporation as a function of time, in accordance with a compartmental model, indicated that observed differences in the accumulation of [(3)H]arachidonate in various phospholipids were probably due to different rates of acylation by arachidonyl-transferases with no appreciable changes in the rates of deacylation by enzymes of the phospholipase A type. Further, the pool of phospholipid-bound arachidonate which is readily available for deacylation-reacylation processes appears to be distributed differentially among various phospholipids with more than 50% of this pool located in phosphatidylinositol and only 0.75% of the phosphatidylinositol molecules appear to be active in deacylation-reacylation processes involving arachidonyl groups.

Effects of insulin and norepinephrine on glucose transport and metabolism in rat brown adipocytes. Potentiation by insulin of norepinephrine-induced glucose oxidation.

Glucose is an important fuel for rat brown adipose tissue in vivo and its utilization is highly sensitive to insulin. In this study, the different glucose metabolic pathways and their regulation by insulin and norepinephrine were examined in isolated rat brown adipocytes, using [6-14C]glucose as a tracer. Glucose utilization was stimulated for insulin concentrations in the range of 40-1000 microU/ml. Furthermore, the addition of adenosine deaminase (200 mU/ml) or adenosine (10 microM) did not alter insulin sensitivity of glucose metabolism. The major effect of insulin (1 mU/ml) was a respective 7-fold and 5-fold stimulation of lipogenesis and lactate synthesis, whereas glucose oxidation remained very low. The 5-fold stimulation of total glucose metabolism by 1 mU/ml of insulin was accompanied by an 8-fold increase in glucose transport. In the presence of norepinephrine (8 microM), total glucose metabolism was increased 2-fold. This was linked to a 7-fold increase of glucose oxidation, whereas lipogenesis was greatly inhibited (by 72%). In addition, norepinephrine alone did not modify glucose transport. The addition of insulin to adipocytes incubated with norepinephrine, induced a potentiation of glucose oxidation, while lipogenesis remained very low. In conclusion, in the presence of insulin and norepinephrine glucose is a oxidative substrate for brown adipose tissue. However the quantitative importance of glucose as oxidative fuel remains to be determined.

Influence of the endothelium on the amplification by serotonin of vasoconstrictor responses to noradrenaline and sympathetic nerve stimulation in rabbit isolated ear artery

The influence of the vascular endothelium on the amplifying effect of serotonin on steady-state responses to noradrenaline (NA) and sympathetic nerve stimulation (SNS) has been studied in the rabbit isolated ear artery. Removal of the endothelium abolished the dilator effect of acetylcholine (ACh, 1 μM) obtained in the presence of NA (0.3 μM). Responses to NA were increased after endothelium removal; however, responses to SNS were unaffected. Serotonin in a concentration which did not itself produce vasoconstriction (100 nM) increased responses of endothelium-intact preparations to NA and SNS and of endothelium-denuded preparations to SNS but had no effect on NA responses of endothelium-denuded preparations. If neuronal uptake was inhibited with cocaine (1 μM), serotonin markedly amplified responses to NA and SNS in both endothelium-intact and endothelium-denuded preparations. These results suggest that the endothelium influences the amplfying effect of serotonin on responses of rabbit ear artery to NA but not to SNS. Inhibition of removal of serotonin and NA by neuronal uptake may extend the facilitatory interaction between NA and serotonin to smooth muscle cells which are not subject to the inhibitory influence of an endothelium derived relaxing factor.

Renal Hemodynamic Effects of Calcium Antagonists

Recently, attention has focused on the effects of calcium antagonists on renal function. When administered in vitro to the isolated perfused kidney, calcium antagonists exhibit consistent actions permitting characterization of their renal effects. Calcium antagonists do not affect the vasodilated isolated perfused kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists markedly augment glomerular filtration rate but produce only a modest improvement in renal perfusion. This preferential augmentation of glomerular filtration rate may be attributable to a selective vasodilation of preglomerular vessels. Although the clinical implications of such observations are not yet clear, preliminary studies in experimental animal models indicate that calcium antagonists may exert salutary effects on renal function in clinical settings that are characterized by impaired renal hemodynamics. The possible benefits of calcium antagonists in ameliorating the development of renal dysfunction in patients in whom there is increased risk for the development of acute renal insufficiency remain to be evaluated.

Voltage-dependent calcium release in guinea-pig cardiac ventricular muscle as antagonized by magnesium and calcium.

An increase in extracellular potassium concentration from 4 to 16 mmol/l caused a decrease in membrane potential from -92 to -59 mV and selectively diminished the earlier of two contraction components of guinea-pig papillary muscles at 0.2 Hz stimulation frequency in the presence of noradrenaline. The influence on the early contraction component had a threshold of 8 mmol/l K+, corresponding to a membrane potential of -77 mV. However, test contractions elicited 800 ms after the 5 s stimulation interval exhibited an unimpaired early component. Since the activator calcium responsible for the early contraction component is derived, in mammalian ventricular muscle, from the junctional sarcoplasmic reticulum, it is assumed that the release site of the reticulum was filled with calcium shortly (800 ms) after a regular contraction, and lost its calcium at 16 mmol/l extracellular K+, during the 5 s stimulation interval. The potassium-induced depolarization determined the rate of calcium leakage during rest from the intracellular store. The depolarization-induced decline of the early contraction component was equally well antagonized by Mg2+ or Ca2+ without influencing the measured transmembrane potential. Both divalent cations shifted the relation between potassium concentration or membrane potential and the strength of the early contraction component to less negative membrane potentials. In order to reduce the early contraction component by 25% in the presence of 9.6 instead of 1.2 mmol/l Mg2+, the potassium concentration had to be increased from 9.6 to 22.0 mmol/l, with a respective decrease in resting membrane potential from -72.6 to -51.1 mV. The antagonistic effect of both divalent cations is though to result from the neutralization of negative charges outside the sarcolemma with a respective decrease in the outside surface potential.

Effects of potassium and norepinephrine on calcium influx in guinea-pig vas deferens

The effects of potassium (K +) and adrenoceptor agonists on 45Ca influx and contraction of isolated vas deferens from reserpine-treated guinea-pigs has been investigated. K + (18–84 mM) increased 45Ca influx with the maximum influx occuring at 50 mM K +. The rate of influx upon exposure to K + was highest in the first 2 min and decreased thereafter. In contrast to K +, norepinephrine, methoxamine and xylazine did not increase the rate of 45Ca influx. Norepinephrine and methoxamine, but not xylazine, inhibited 45Ca influx induced by high K +. The inhibitory effect of norepinephrine was also present in denervated tissues. Prazosin, but not yohimbine or propranolol, blocked the inhibitory effect of norepinephrine. Potassium-induced contractions were significantly potentiated in the presence of norepinephrine, especially at low calcium concentrations. We conclude that K + contracts the guinea-pig vas deferens by increasing the influx of calcium whereas stimulation of α 1-adrenoceptors 45Ca influx elicited by high potassium.

The search for a hypothalamic Na+,K+-ATPase inhibitor.

Accumulating experimental evidence suggests that natriuresis in response to intravascular volume expansion is promoted by an endogenous regulator of Na+,K+-adenosine triphosphatase (ATPase). Efforts to purify this substance by a number of laboratories have as yet been unsuccessful. The properties of partially purified inhibitors from plasma, urine, and tissue often fail to possess the characteristics thought to be consistent with those of a physiological regulator. These include potency (Ki of approximately 1 nM), reversibility of inhibition, specificity for Na+,K+-ATPase, and responsiveness to relevant physiological stimuli. Two rather different candidate substances, extracted from urine and hypothalamus, have been purified to a high degree. Neither is a peptide, and both are of low molecular weight and resistant to acid hydrolysis. The substance from urine is rather nonpolar and interacts with digoxin-specific antibodies, while that from hypothalamus is polar and does not appear to share epitopes with the cardiac glycosides. On the serosal surface of the toad urinary bladder, the hypothalamic substance causes a reversible inhibition of Na+ transport, inhibits rubidium uptake in red blood cells by acting on the membrane's exterior surface, inhibits binding of ouabain to purified Na+,K+-ATPase, and reversibly inhibits hydrolysis of adenosine 5'-triphosphate by the enzyme with a Ki of 1.4 nM. The hypothalamic inhibitor may be differentiated from ouabain by their respective ionic requirements for optimal inhibition of enzymatic activity, and although both ouabain and the hypothalamic inhibitor fix Na+,K+-ATPase in its E2 conformation, the hypothalamic inhibitor does not promote phosphorylation of the enzyme by inorganic phosphate in the presence of Mg2+. Ionic requirements for inhibition also differentiate the hypothalamic inhibitor from vanadate ion, as does the inhibitor's activity in the presence of norepinephrine. Further enzymological and physiological studies will be facilitated by structural characterizations of the inhibitory substances and by the availability of a method to measure their concentrations in physiological fluids.

Renal hemodynamic effects of calcium antagonists

Although the cardiovascular actions of calcium antagonists have been studied extensively, it is only recently that attention has focused on the effects of calcium antagonists on renal function. Variable actions of calcium antagonists on renal hemodynamics have been observed when these agents are used in experimental animal models. In contrast, when administered in vitro to the isolated perfused kidney, calcium antagonists demonstrate more predictable actions. Calcium antagonists do not affect the vasodilated isolated kidney, but they do dramatically alter the response of the kidney to vasoconstrictor agents. In the presence of norepinephrine, calcium antagonists produce a modest improvement in renal perfusion and significantly augment glomerular filtration rate. This preferential augmentation of glomerular filtration rate may be attributable to a selective vasodilation of pre-glomerular vessels. Although the clinical implications of such observations are not yet clear, preliminary studies indicate that calcium antagonists may exert salutary effects on renal function in clinical settings that are characterized by impaired renal hemodynamics. The possible benefits of calcium antagonists in ameliorating the development of renal dysfunction in patients in whom there is increased risk for the development of acute renal insufficiency remain to be evaluated.

Acute Δ9-tetrahydrocannabinol exposure: Effects of hypothalamic-pituitary-testicular activity in mice

The endocrine functions of the median eminence, pituitary and testes were examined in the male mice after exposure to Δ 9-tetrahydrocannabinol (THC) either in vivo or in vitro. The secretion of luteinizing hormone-releasing hormone (LHRH) under basal conditions, and in the presence of norepinephrine (NE; 60μM), was significantly enhanced in median eminence fragments obtained 1 hr post-treatment with THC (50 mg/kg), while addition of THC (250 ng/ml) to the incubation media enhanced clonidine, as well as NE-stimulated LHRH release, but did not affect basal LHRH release. In vitro exposure to THC also enhanced LHRH-stimulated LH release by pituitaries, but did not affect basal secretion rates. In vivo THC exposure tended to enhance pituitary responsiveness to LHRH, although this effect was not statistically significant. In testicular perifusions, addition of THC at a concentration of 250 ng/ml completely blocked hCG-stimulated T secretion within 30 min. The suppressive effects of a lower dose of THC, 25 ng/ml, required 60 min to inhibit T production, an affect which persisted for 60–80 min post-THC. These findings indicate that THC exposure enhances responsivity at neuroendocrine target sites, but attenuates gonadotropin-stimulated testicular steroidogenesis.

Triggered rhythms in atrial muscle

Intracellular and extracellular recording techniques were used to study triggered activity in tissues isolated from the inferior right atrium of the dog. In the presence of norepinephrine (>10 −7 M) single stimuli or short rapid pacing elicited action potentials with delayed after-depolarizations, leading to single or repetitive non-driven beats. Most commonly, during sustained triggered activity action potential and electrogram configurations remained constant. In addition, cycle length changed gradually, initially decreasing and then increasing before activity stopped. However in some preparations, once sustained triggered activity was initiated there were abrupt spontaneous changes in action potential and electrogram configurations that were coincident with abrupt spontaneous changes in cycle length. When quiescent, short rapid pacing caitiated triggered activity with a relatively short cycle length that abruptly shifted to a longer cycle length before stopping. During sustained triggered activity, short rapid pacing caused an abrupt decrease in cycle length that was coincident with changes in action potential and electrogram configurations. The present results indicate that abrupt changes in cycle length can occur during bouts of triggered activity resulting in unique patterns of arrhythmias. These rhythms may be due to interactions and shifts between multiple sites of triggered pacemaker activity.

Effects of noradrenaline exposure on rat brown adipocytes in cultures. An ultrastructural study

Adipocytes in intact brown adipose tissue show multivacuolar lipid deposit and mitochondria of ‘typical’ morphology. Cultured brown adipocytes retain the multivacuolar lipid deposit, while ‘typical’ mitochondria degenerate and ‘atypical’ organelles appear instead of the former. Since evidence exists that catecholamines deeply influence brown adipose tissue morphology and function in vivo, we undertook the present ultrastructural investigation to assess whether exposure of cultured brown fat cell to noradrenaline could prevent (or induce regression of) the in vitro morphological modifications of brown adipocytes. Brown adipocytes cultured for 8 h in the presence of noradrenaline (5 × 10 −5 M) had a larger mitochondrial area (i.e. a larger percentage of cytoplasm occupied by non-degenerating mitochondria) in comparison with control cells, as assessed by morphometry; this was due to larger number of mitochondria in noradrenaline-treated cells. Moreover, a number of cells with mitochondria strictly resembling those of the intact tissue were visible in noradrenaline-treated cultured after 8 hr, while ‘typical’ mitochondria were no longer observed in parallel control cultures. After 5 days of culture without hormone addition, exposure to noradrenaline (5 × 10 −5 M) did not induce quantitative modifications of ‘atypical’ mitochondria or changes of their ultrastructure up to 12 hr. However, reduction in size of the lipid deposit and activation of both rough endoplasmic reticulum and Golgi apparatus were evident in noradrenaline-treated adipocytes in comparison with nontreated cells.

Modification of the renal hemodynamic response to vasoconstrictors by calcium antagonists.

Theoretical considerations suggest that the renal response to calcium antagonists may vary depending on the factors influencing basal vascular tone. Studies were conducted using the isolated perfused rat kidney to determine the response to calcium antagonists under conditions in which the determinants of renal vascular tone were accurately defined. With this model, calcium antagonists elicit vasodilation only in the presence of a vasoconstrictor. In this setting, however, the degree of vasodilation elicited depends on the nature of the vasoconstrictor employed. Thus, the reduction in renal perfusate flow (RPF) elicited by KCl-induced depolarization was completely reversed by the calcium antagonist, nitrendipine. In contrast, identical levels of vasoconstriction elicited by norepinephrine or angiotensin II were only partially reversed, suggesting that these agonists activate the renal vasculature by mechanisms that are more complex than membrane depolarization. Examination of the response of glomerular filtration rate (GFR) revealed that in the presence of norepinephrine and angiotensin II, nitrendipine exerted a preferential augmentation of GFR. Thus, concentrations that produced only modest effects on RPF increased GFR to levels equal to or exceeding control values. This selective augmentation of GFR did not occur during the renal vasoconstriction elicited by KCl. It is proposed that renal microvessels exhibit regional heterogeneity in regard to activation mechanisms and sensitivity to calcium antagonists. Calcium antagonists may selectively attenuate agonist-induced vasoconstriction of preglomerular vessels.

Nitroglycerin-sensitive and -resistant contractions mediated by receptor-operated calcium channels in rabbit ear artery.

In isolated rabbit ear arteries incubated in a Ca2+-free medium with EGTA and nifedipine in the presence of norepinephrine, serotonin or histamine, an addition of Ca2+ induced a tonic contraction which is due to Ca2+ entry through receptor-operated Ca2+ channels (ROCs). Nitroglycerin (10(-4) M) significantly inhibited the ROCs-dependent contractions produced by serotonin or histamine, but failed to inhibit the ROCs-dependent contraction by norepinephrine. These results suggest the possible existence of two types of receptor-operated Ca2+ channels in rabbit ear artery.