A Comparison of Ectonucleotidase Activities on Vascular Endothelial and Smooth Muscle Cells<sup>a</sup>

Slakey, Linda L.; Gordon, Ellen L.; Pearson, Jeremy D.

doi:10.1111/j.1749-6632.1990.tb37686.x

Cited by 35 publications

(14 citation statements)

References 11 publications

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“…Although, in preliminary experiments, we failed to find GTP in the material secreted during trichocyst exocytosis, rapid extracellular hydrolysis of GTP may have occurred. Paramecium, like some animal cells (14), has a potent ectonucleoside triphosphatase activity (K.D.C., unpublished data). Whereas this activity is clearly not necessary for the short-term response or adaptation (see Fig.…”

Section: Discussionmentioning

confidence: 99%

External GTP alters the motility and elicits an oscillating membrane depolarization in Paramecium tetraurelia.

Clark

Hennessey

Nelson

1993

Proc. Natl. Acad. Sci. U.S.A.

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Paramecium, a unicellular ciliated protist, alters its motility in response to various stimuli. Externally added GTP transiently induced alternating forward and backward swimming interspersed with whirling at a concentration as low as 0.1 jFM. ATP was 1000-fold less active, whereas CTP and UTP produced essentially no response. The response to the nonhydrolyzable GTP analogs guanosine 5'-[y-thio]triphosphate and guanosine 5'-[13,y-imido]triphosphate was indistinguishable from that to GTP. This behavioral response was correlated with an unusual transient and oscillating membrane depolarization in both wild-type cells and the mutant pawn B, which is defective in the voltage-dependent Ca2+ current required for action potentials. This is a specific effect of external GTP on the excitability of a eukaryotic cell and, to our knowledge, is the first purinergic effect to be discovered in a microorganism.Paramecium tetraurelia normally swims forward except for occasional brief periods of backward swimming or whirling, a randomly directed motion (1). However, many stimuli, thermal, electrical, mechanical, or chemical, can alter the swimming speed and the frequency and duration of backward swimming and whirling events (2-6). These responses are normally transient. Cells return to their prestimulus behavior even in the continued presence of the stimulus, a form of sensory adaptation. The combination of behavioral response and subsequent adaptation can result in attraction to or repulsion from a stimulus (6). These swimming behaviors generally have clear, well-studied, and readily measurable electrophysiological correlates that can aid in unraveling a signal-transduction pathway. For example, increased swimming speed is correlated with membrane hyperpolarization, whereas decreased swimming speed is correlated with membrane depolarization. Strong depolarizations can elicit graded Ca2+-based action potentials, resulting in whirling and backward swimming due to increased intraciliary Ca2+ (3,4).To quantify these swimming behaviors, we have developed a computerized motion analysis assay that measures the percentage of total path time spent whirling and undergoing transitions between forward and backward swimming [defined as percent directional changes (PDCs) (1)]. While using this assay to quantify the behavioral effects of externally added nucleotides, we found that guanine nucleotides specifically and potently altered the swimming behavior of paramecia. In addition, while attempting to corroborate the GTP-induced behavior of the cell with changes in membrane potential, we discovered an electrophysiological response.

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Section: Discussionmentioning

confidence: 99%

External GTP alters the motility and elicits an oscillating membrane depolarization in Paramecium tetraurelia.

Clark

Hennessey

Nelson

1993

Proc. Natl. Acad. Sci. U.S.A.

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“…Also, our recent work using cultured endothelial and smooth muscle cells isolated from the caudal artery of rats indicates that the main source of the released purines is the endothelium and to a lesser extent, smooth muscle [11]. As ATP is degraded fairly rapidly to ADP, AMP and adenosine in vascular tissues, probably through hydrolysis by ectonucleotidases [8, 12], the origin of released purine is considered to be ATP. Indeed, Shinozuka et al [11] have shown that the amount of measured ATP released by noradrenaline from the caudal arteries of rats was increased by the 5′-nucleotidase inhibitor, α, β-methylene ADP.…”

Section: Introductionmentioning

confidence: 99%

Antihypertensive Effect of All-cis-5,8,11,14,17-Icosapentaenoate of Aged Rats Is Associated with an Increase in the Release of ATP from the Caudal Artery

Hashimoto¹,

Shinozuka²,

Hossain³

et al. 1998

J Vasc Res

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Fish oils have been shown to lower blood pressure in hypertensive subjects. All-cis-5,8,11,14,17-icosapentaenoate (EPA), one of the ω–3 polyunsaturated fatty acids, is known to be one of the major active components in fish oil that has beneficial effects on the cardiovascular system. However, little is known about the antihypertensive effect of EPA alone on blood pressure. In the present study, we have determined the spontaneous and noradrenaline-evoked release of ATP, ADP, AMP, and adenosine from caudal arteries of aged (100 weeks old) Wistar rats which were fed a standard diet or a high cholesterol diet, treated with EPA. Dietary EPA administration increased plasma and caudal arterial EPA concentrations and repressed increases in blood pressure with advancing age in both aged rats with and without hypercholesterolemia. In addition, noradrenaline (1 µmol/l) evoked a significantly greater release of purines from the caudal arteries of EPA-administered aged rats compared to both sets of control rats. Regression analysis revealed a significant relationship between the total amount of purines released from the artery and blood pressure. These results suggest that administration of EPA to aged rats increases the release of ATP from the vascular endothelial cells, leading to repression of the blood pressure rise seen with advancing age.

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“…Studies with ATP are complicated by its rapid dephosphorylation by ectonucleotidases present on smooth muscle preparations, to give adenosine which has its own effects (Slakey et al, 1990).…”

Section: Introductionmentioning

confidence: 99%

Characterization of P₁‐purinoceptors on rat duodenum and urinary bladder

Nicholls

Hourani

Kitchen

1992

British J Pharmacology

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1 The P1-purinoceptors mediating relaxation of the rat duodenum and inhibition of contraction of the rat urinary bladder were characterized by use of adenosine and its analogues 5'-N-ethylcarboxamidoadenosine (NECA), N6-cyclopentyladenosine (CPA) and 2-p-((carboxyethyl)phenethylamino) -5'-carboxamidoadenosine (CGS 21680), as well as the Al-selective antagonist 1,3-dipropyl-8-cyclopentylxanthine (DPCPX). The stable analogue of adenosine 5'-triphosphate (ATP), adenylyl 5'-(fi,y-methylene)diphosphonate (AMPPCP), was also used as previous work had indicated that it has a direct action on some P1 receptors in addition to its P2-purinoceptor activity. 2 In the rat duodenum, the order of potency of the adenosine agonists was NECA > CPA > AMPPCP = adenosine > CGS 21680, and DPCPX antagonized CPA and AMPPCP at a concentration of 1 nm whereas equivalent antagonism of NECA and adenosine required a concentration of 1 ym. This suggests the presence of a mixture of A1 and A2 receptors in this tissue, with CPA and AMPPCP acting on the A1 and NECA and adenosine acting on the A2 receptors. 3 In the rat bladder, the order of potency of the adenosine agonists for inhibition of carbachol-induced contractions was NECA > adenosine > CPA = CGS 21680, and a concentration of DPCPX of 1 $M was required to antagonize responses to NECA and adenosine. This suggests the presence of A2 receptors in this tissue. ATP and AMPPCP each caused contractions which were not enhanced by DPCPX (1 M) which suggests that in this tissue AMPPCP was acting only via P2 receptors and had no P1 agonist activity. That AMPPCP was active on the A1 receptors in the duodenum but inactive on the A2 receptors in the bladder implies that it has selectivity for the A1 subtype.4 That CGS 21680, which has been reported to bind selectively to the high affinity A2a subclass of A2 receptors, had a very low potency on the A2 receptors in the duodenum and in the bladder suggests that these receptors are of the low affinity A2b subclass.

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A Comparison of Ectonucleotidase Activities on Vascular Endothelial and Smooth Muscle Cells^a

Cited by 35 publications

References 11 publications

External GTP alters the motility and elicits an oscillating membrane depolarization in Paramecium tetraurelia.

External GTP alters the motility and elicits an oscillating membrane depolarization in Paramecium tetraurelia.

Antihypertensive Effect of All-cis-5,8,11,14,17-Icosapentaenoate of Aged Rats Is Associated with an Increase in the Release of ATP from the Caudal Artery

Characterization of P₁‐purinoceptors on rat duodenum and urinary bladder

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A Comparison of Ectonucleotidase Activities on Vascular Endothelial and Smooth Muscle Cellsa

Cited by 35 publications

References 11 publications

External GTP alters the motility and elicits an oscillating membrane depolarization in Paramecium tetraurelia.

External GTP alters the motility and elicits an oscillating membrane depolarization in Paramecium tetraurelia.

Antihypertensive Effect of All-cis-5,8,11,14,17-Icosapentaenoate of Aged Rats Is Associated with an Increase in the Release of ATP from the Caudal Artery

Characterization of P1‐purinoceptors on rat duodenum and urinary bladder

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A Comparison of Ectonucleotidase Activities on Vascular Endothelial and Smooth Muscle Cells^a

Characterization of P₁‐purinoceptors on rat duodenum and urinary bladder