Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Tachyphylaxis”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 847 records · Page 47Linked to original sources
PubMed1985

Thyrotropin-releasing hormone effects on guinea pig antrum.

Thyrotropin-releasing hormone transiently increased resting tension and spontaneous contraction amplitude more potently in longitudinal muscle than in circular muscle. The frequency of the contraction did not change. Excitation was enhanced by eserine, and blocked by atropine and tetrodotoxin; this excitation was, therefore, probably mediated by acetylcholine release from cholinergic neurons in the myenteric plexus. In the presence of atropine, thyrotropin-releasing hormone (10(-10) M) inhibited spontaneous contraction, particularly in longitudinal muscle. This was accompanied by decreased resting tension at and above 10(-8) M. Because contraction was not blocked by adrenergic blockade, indomethacin, methysergide, or hexamethonium, but was abolished by tetrodotoxin, it was postulated that thyrotropin-releasing hormone might stimulate nonadrenergic, noncholinergic inhibitory neurons. There was no cross-tachyphylaxis between 5-hydroxytryptamine and thyrotropin-releasing hormone. Results show that 5-hydroxytryptamine does not interact with thyrotropin-releasing hormone.

Acetylcholine↗
PubMed1975

The effects of some natural prostaglandins on isolated human circular bronchial muscle.

PGE1 relaxed isolated human circular bronchial muscle over a wide concentration range as did isoprenaline. Surprisingly isoprenaline was more potent than PGE1. PGF2alpha weakly contracted this muscle preparation whereas histamine was more potent. PGE2, however, produced paradoxical results, relaxing some tissues and contracting others, always in a concentration-related manner irrespective of tissue tone. In preparations that contracted to PGE2, tachyphylaxis induced to PGF2alpha also applied to PGE2, but did not affect PGE1 relaxations of histamine contractions. These findings suggest that pge2 can stimulate either PGF2alpha or PGE1 receptors of isolated human bronchial muscle.

Bronchi↗
PubMed1979

Timolol--further observations.

Data from clinical records of patients using timolol confirm the ocular hypotensive effect of the drug in secondary glaucoma, aphakic glaucoma, ocular hypertension, and when used in combination with various other forms of glaucoma therapy. No serious local or systemic side effects were noted. Although many adrenergic agents ultimately produce tachyphylaxis, this effect is infrequent in timolol therapy.

Carbonic Anhydrase Inhibitors↗
PubMed1999

Procaine excites nociceptors in cultures from dorsal root ganglion of the rat.

Procaine, a classical local anesthetic, produces, at low concentration (2-200 microM), excitation in a distinct population of small sensory neurons isolated from newborn rats (2D) and cultured for 1-5 days. The excitation or inward current (>50 pA) induced by procaine was observed in 59 out of 78 neurons. Nearly all these procaine-sensitive neurons (56 of 59) were also sensitive to capsaicin while 8 procaine-insensitive neurons responded to capsaicin (1 microM). In procaine-sensitive neurons tested for responsiveness to noxious heat, a 10 s temperature ramp from 24 to 48 degrees C induced an inward current of 413 +/- 47 pA (SEM, n = 27) and this current was enhanced, in the presence of procaine, about 3-fold (2.8 +/- 0.4, SEM, n = 27). The responses to procaine were concentration dependent and underwent pronounced tachyphylaxis after repeated applications. The voltage-current relationship exhibited outward rectification and the apparent reversal at 25 +/- 4.2 mV (SEM, n = 9) suggesting that the current is carried by cations including Ca2+. This procaine effect may offer an explanation for toxic consequence of the clinical use of local anesthetics.

Anesthetics, Local↗
PubMed1999

Nerve growth factor acutely sensitizes the response of adult rat sensory neurons to capsaicin.

Perforated patch clamp recordings were made from 118 voltage clamped (-60 mV), capsaicin-responsive dorsal root ganglion (DRG) cells (<30 microns) maintained in dissociated cell culture (6-24 h). A second puff of capsaicin 10 min later always evoked a substantially smaller inward current than the initial puff (tachyphylaxis). Bath-application of NGF (2, 10 or 100 ng/ml) during the 10-min interval resulted in facilitation of the second response in a dose dependent manner in 67% of cells studied. NT-4/5 exerted similar effects but NT-3 did not. Ten minute pretreatment with NGF increased the initial response to capsaicin. We conclude that NGF acutely conditions the response to capsaicin via direct action on DRG cells. Since the capsaicin receptor (VR1) mediates noxious heat sensitivity of polymodal nociceptors, acute sensitization of the noxious heat response by NGF and NT-4/5 may involve a direct action on VR1.

Animals↗
PubMed1997

Multiple vasoactive factors in epidermal secretions of the Arabian Gulf catfish, Arius bilineatus (Valenciennes).

1. The Arabian Gulf catfish produces proteinaceous epidermal secretions when threatened or injured. 2. The soluble fraction of the catfish epidermal secretions (SES) has vasoconstrictor activities on sheep renal arteries, which can be inhibited by several antagonists, including atropine, indomethacin, prazosin, and verapamil. 3. Mepyramine, yohimbine, and ketanserin have negligible effects on SES-induced contraction. 4. SES exhibits a significant tachyphylaxis upon addition of a second (8.4% reduction) and third (47% reduction) dose of SES to the organ bath, which can be partially prevented by addition of a fresh arterial section prior to each addition. 5. A vasoconstricting activity has been partially purified from SES by gel filtration on Fractogel HW-65(F) and appears to be a protein with a pI near 7.3. This activity is affected only by verapamil and prazosin.

Animals↗
PubMed1997

Cardiovascular pharmacology of aqueous extract of the leaves of Bridelia atroviridis Muell. Arg. (Euphorbiaceae) in the rat.

Lyophilised decoction (10%) of the leaves of Bridelia atroviridis Muell. Arg. (Euphorbiaceae) was studied in the rat cardiovascular system. In vivo, the extract (15 and 30 mg/kg) caused a decrease of arterial pressure and a decrease of heart rate in an anaesthetized rat (ethylcarbamate 1.2 g/kg). If administrations of Bridelia were repeated (three times) a tachyphylaxie phenomena was observed. After administrations of adrenaline, noradrenaline, acethylcholine and isoprenaline the extract had no effect on the action of these neuromediators on blood pressure. In vitro the extract induced dose-dependent negative inotropic and chronotropic effects in isolated rat heart. It was ineffective in rat aorta preparations. Bridelia seemed to have a direct effect on rat heart. Hypotension is not due to an action on the vessels. The extract did not appear to interact with adrenergic nor cholinergic receptors. However, the extract was able to potentiate barium chloride induced contractions of rat aorta preparations. The extract might act through potential dependent calcium channels.

Animals↗
PubMed2001

Attenuation of endothelin-1 induced vasoconstriction by 17beta estradiol is not sustained during long-term therapy in postmenopausal women with coronary heart disease.

OBJECTIVES: The goal of this study was to determine the long-term effects of estrogen replacement therapy on the response to endothelin-1 (ET-1) in postmenopausal women with coronary heart disease. BACKGROUND: It is thought that the vasoconstrictor ET-1 is involved in the development and progression of atherosclerosis. Estrogen replacement may slow the development of atherosclerosis in postmenopausal women. METHODS: Nineteen of 20 postmenopausal women randomized to either three months of 2 mg oral estradiol or placebo completed the double-blind placebo-controlled protocol. Change in forearm blood flow (FBF) in response to a 60 min brachial arterial infusion of ET-1 (5 pmol/min) was measured before randomization, after one month of randomized therapy and after three months of therapy using venous occlusion plethysmography. RESULTS: Estrogen treatment had no effect on baseline FBF. Systolic and diastolic blood pressure and heart rate did not change in response to estrogen therapy or ET-1. Before randomization, in response to ET-1, FBF was reduced by -21.9% (mean response over 60 min) in the placebo group and -19.0% in the estradiol group (p = 0.67). After one month of therapy, the response was attenuated in the estrogen group, -10.0%, compared with the placebo group, -23.6 (difference in means 13.6%, 95% confidence interval [0.7%, 26.6%], p = 0.041). After three months of therapy, there was no difference in response between the placebo group, -27.0%, and estrogen group, -30.2% (p = 0.65). CONCLUSIONS: In postmenopausal women with coronary heart disease, estrogen therapy inhibits the vasoconstrictor response to ET-1 after one month of therapy. This effect is lost after three months of therapy, suggesting that tachyphylaxis to one potentially beneficial action of estradiol develops during chronic treatment.

Aged↗
PubMed2003

Synthesis and pharmacological characterization of a new benzoxazole derivative as a potent 5-HT3 receptor agonist.

N-(2-Benzoxazol-2-yl-ethyl)-guanidine hydrochloride (10) was synthesized and pharmacologically tested. This compound showed high affinity for the 5-HT(3) receptor (K(i)=0.77 nM) and potently triggered the von Bezold-Jarisch reflex (BJR) in rats with an ED(50)=0.52 microg/kg iv and intrinsic activity next to 1 (i.a.=0.94). This stimulant effect was abolished by pretreatment with the 5-HT(3) receptor antagonist granisetron and was subject to a rapid and pronounced tachyphylaxis, due to desensitization of the peripheric cardiac 5-HT(3) receptor. Consequently, 10 acts as an in vivo 5-HT(3) antagonist inhibiting the BJR responses evoked by submaximal doses of 5-HT with an ID(50)=5.8 microg/kg iv.

Animals↗
PubMed1999

Methodologic aspects of acetylcholine-evoked relaxation of rabbit aorta.

The acetylcholine-evoked relaxation of rabbit isolated thoracic aorta precontracted by phenylephrine was studied. Phenylephrine caused a steady contraction that was maintained for 6 h. In the presence of calcium disodium ethylenediaminetetraacetate (EDTA) and ascorbic acid the contraction decreased with time. N(G)-Nitro-L-arginine abolished the inhibitory effect of EDTA and ascorbic acid. Acetylcholine evoked a rapid concentration-dependent relaxation that recovered spontaneously and slowly, but fully, with time. Relaxation evoked by equieffective concentrations of carbachol and acetylcholine had the same time course. Cumulative addition of acetylcholine (10(-7)-3 x 10(-5) M) caused a marked relaxation that was reverted slightly at high concentrations. The relaxation was the same with rings derived from the upper, middle, and lower part of the thoracic aorta. Two consecutive concentration-response curves for acetylcholine obtained at a 2-h interval demonstrated a slight development of tachyphylaxis. The relaxation was inversely related to precontractile tension evoked by phenylephrine when expressed as a percentage, but independent when expressed as g tension. Storage of aorta in cold salt solution for 24 h did not alter the relaxation. EDTA and ascorbic acid did not alter the relaxation. It is concluded that (1) EDTA and ascorbic acid can not be used with impunity to stabilize catecholamines used as preconstriction agents; (2) the reversal of the acetylcholine-evoked relaxation is not due to hydrolysis of acetylcholine; (3) the relaxation is uniform in all segments of thoracic aorta; (4) cold storage of aorta does not alter the relaxation; and (5) acetylcholine releases the same amount of relaxing factor, irrespective of the precontractile tension.

Acetylcholine↗
PubMed1978

Effect of toxic thioureas on resistance of rats to growth in the lungs of intravenously and intratracheally seeded tumour cells.

Clonogenic growth (colony-forming efficiency, CFE) of i.v. injected allogeneic W256 tumour cells in the lungs was markedly enhanced by treatment of rats with alpha-naphthyl thiourea (ANTU) injected i.p. from 2 h before to 2 h after the tumour cells. ANTU specifically increases pulmonary vascular permeability in adult rats and causes acute pulmonary oedema and pleural effusion. Inhibition of drug toxicity to the lungs by tachyphylaxis, specific antimetabolites or iodides did not abolish the effect of ANTU on CFE. CFE was not increased when cells were seeded by i.v. injection the lungs affected by advanced pulmonary oedema at 6 to 24 h after treatment with drug. ANTU did not enhance growth of intratracheally injected cells. Although ANTU has no cytotoxic or immunosuppressive action, treatment of tumour-immunized rats with ANTU caused apparent "breakdown" of tumour immunity in 50% of rats, by causing growth of tumour colonies in the lungs. Possible mechanisms for the ANTU-induced decrease in innate resistance to growth of tumour in the lungs are discussed.

Adrenalectomy↗
PubMed1983

Constant kinetics and constant concentration-effect relationship during long-term beta-blockade with pindolol.

Long-term beta-blockade is said to increase the number of beta-receptors. The effect of beta-blockers could therefore be reduced after long use. We tested this hypothesis in nine healthy subjects given 15 mg pindolol daily for 4 wk. Plasma concentrations (measured fluorometrically), isoproterenol dose-response relationship (to calculate the dose needed to increase heart rate by 25 bpm), renin, epinephrine, and norepinephrine were measured several times before and after the first and last dose. Kinetic parameters remained stable: total clearance (Cltot) = 45.2 and 42.9 l/hr, and Vdss = 205.8 and 198.6 l after the first and last dose. The concentration-effect relationship, plotted as the "dose ratio minus one" against the log of the plasma concentration was identical after 4 wk. Basal plasma renin activity was reduced slightly and the increase of stimulated plasma renin was blunted by pindolol even after 4 wk. The initial lowering of unstimulated renin by pindolol in the first 2 hr after dosing was not detectable after 4 wk. Epinephrine and norepinephrine levels in plasma were not changed initially nor after 4 wk. It is concluded that pindolol has a stable kinetic profile over time and that its beta-blockade does not induce tachyphylaxis.

Adult↗
PubMed1999

Enhanced delivery of carboplatin into brain tumours with intravenous Cereport (RMP-7): dramatic differences and insight gained from dosing parameters.

Cereport (RMP-7) is a selective bradykinin B2 receptor agonist which increases the permeability of the 'blood-brain tumour barrier' (BBTB) to increase delivery of chemotherapeutic agents to brain tumours. A series of experiments was performed in an RG2 rodent model of glioma to evaluate and refine intravenous (i.v.) parameters to optimize Cereport's clinical utility. The first experiment demonstrated that while carboplatin levels were increased by twofold when given as a bolus during the Cereport infusion, no increase in carboplatin levels were seen when Cereport and carboplatin were simultaneously co-infused for 15 min. A subsequent experiment established that a major factor responsible for the lack of an effect with the co-infusion paradigm was tachyphylaxis to Cereport during the 15 min infusion, for a progressively diminished response to Cereport occurred over that time frame, as plasma levels of carboplatin were rising. A final experiment adjusted the timing of the Cereport and carboplatin infusions so that higher plasma carboplatin levels were achieved prior to initiating the Cereport infusion. Significant uptake effects were achieved when the carboplatin infusion preceded the Cereport infusion by 10 min (i.e. 5 min overlap in the delivery of the two agents). Collectively, these data provide the first systematic evaluation of dosing parameters involving receptor-mediated changes in BBTB permeability and provide new information regarding the pharmacodynamics and potential clinical use of Cereport.

Animals↗
PubMed1999

Evidence that the ATP-induced increase in vasomotion of guinea-pig mesenteric lymphatics involves an endothelium-dependent release of thromboxane A2.

1. Experiments were made to investigate mechanisms by which adenosine 5'-trisphosphate (ATP) enhanced vasomotion in mesenteric lymphatic vessels isolated from young guinea-pigs. 2. ATP (10-8 - 10-3 M) caused a concentration-dependent increase of perfusion-induced vasomotion with the endothelium mediating a fundamental role at low ATP concentrations (10-8 - 10-6 M). 3. The response to 10-6 M ATP showed tachyphylaxis when applied at intervals of 10 min but not at intervals of 20 or 30 min. 4. Suramin (10-4 M) or reactive blue 2 (3x10-5 M) but not PPADS (3x10-5 M) abolished the excitatory response to 10-6 M ATP confirming an involvement of P2 purinoceptors. 5. The excitatory response to 10-6 M ATP was abolished by treatment with either pertussis toxin (100 ng ml-1), antiflammin-1 (10-9 M), indomethacin (3x10-6 M) or SQ29548 (3x10-7 M), inhibitors of specific G proteins, phospholipase A2, cyclo-oxygenase and thromboxane A2 receptors respectively. 6. ATP simultaneously induced a suramin-sensitive inhibitory response, which was normally masked by the excitatory response. ATP-induced inhibition was mediated by endothelium-derived nitric oxide (EDNO) as the response was abolished by NG-nitro-L-arginine (L-NOARG; 10-4 M), an inhibitor of nitric oxide synthase. 7. We conclude that ATP modulates lymphatic vasomotion by endothelium-dependent and endothelium-independent mechanisms. One of these is a dominant excitation caused through endothelial P2 purinoceptors which because of an involvement of a pertussis toxin sensitive G-protein may be of the P2Y receptor subtype. Their stimulation increases synthesis of phospholipase A2 and production of thromboxane A2, an arachidonic acid metabolite which acts as an endothelium-derived excitatory factor.

Adenosine Triphosphate↗
PubMed1999

No reduction in the sufentanil requirement of elderly patients undergoing ventilatory support in the medical intensive care unit.

The aim of the study was to test the hypothesis that the requirement of sufentanil is reduced in elderly patients when the opiate is primarily used to facilitate mechanical ventilation in a medical intensive care unit. A further aim was to study whether elderly patients developed withdrawal symptoms after discontinuing prolonged sufentanil administration. We have studied prospectively two groups of patients requiring mechanical ventilation for more than 96 h; group 1 age < 60 years (n = 316 or 68%) and group 2 age > 70 years (n = 150 or 32%). In all patients sufentanil and midazolam were administered continuously in order to facilitate ventilatory support. After an initial intravenous bolus injection of sufentanil 3.0-8.0 micrograms kg-1, the dosage was adjusted to the patients needs (0.75-1.0 microgram-1 kg-1 h) using a modified Ramsey score by accepting between 3b and 4a as the end point. The amount of sufentanil administered and side effects were recorded at 24-h intervals. Seventy-two hours following the start of sedation with sufentanil/midazolam the dose of sufentanil required for sedation increased significantly (P < 0.05) in both groups when compared with the first 24 h. There was no statistical difference between the two groups in sufentanil requirement at any time during the study. This suggests that tachyphylaxis develops to a similar degree in patients in both age groups. In addition, weaning in the elderly was characterized by a similar degree of withdrawal-like symptoms suggesting that independent of age, there are similar receptor related reactions once the opiate is withdrawn.

Aged↗
PubMed1999

Angiotensin II in human veins: development of rapid desensitization and effect of indomethacin.

1. The present study investigated whether rapid desensitization (tachyphylaxis) develops after exposure of human hand veins to angiotensin (Ang)II and whether pretreatment with indomethacin affects its development. 2. Venoconstrictor responses to increasing (2-256 ng/min) and constant (50 ng/min) doses of AngII and noradrenaline (NA) infusion were obtained in six healthy male subjects using the dorsal hand vein technique. After pretreatment with indomethacin and placebo, venoconstrictor responses to 50 ng/min AngII infusion were obtained in eight healthy male subjects. 3. The maximal mean (+/- SD) venoconstrictor response to NA (obtained with 256 ng/min NA) was 93.1 +/- 4.7%, whereas that to AngII (obtained with doses between 16 and 128 ng/min) was 43.8 +/- 12.2%. Continuous infusion of NA induced constant venoconstriction, whereas the venoconstrictor response to AngII peaked 3 min after the beginning of infusion and, thereafter, was attenuated. 4. Venoconstriction in response to constant AngII infusion after indomethacin pretreatment was significantly larger than that after placebo from 6 to 18 min after the initiation of infusion. 5. These findings show that rapid desensitization to AngII develops in human hand veins and this is compatible with the hypothesis that vasodilator prostaglandins are involved in the development of this desensitization.

Adult↗
PubMed1981

Effects of 5-hydroxytryptamine and ergotamine on human superficial temporal artery.

Isometric tension was recorded in ring preparations of human superficial temporal arteries contracted by noradrenaline (NA), 5-hydroxytryptamine (5-HT), and ergotamine. In contrast to NA and 5-HT, ergotamine induced long-lasting contractions refractive to additional stimulations and resistant to repeated wash-out. When tested against 5-HT, ergotamine acted as a non-competitive antagonist. When repeating the 5-HT stimulations (4.7 x 10(-5) M) the contractile response decreased indicating tachyphylaxis to this agent. As ergotamine revealed both a vasoconstrictive and a 5-HT-blocking activity, the beneficial effect in migraine may be by an interference during both the vasoconstrictory and vasodilatory phases.

Adult↗
PubMed1996

Erythromycin inhibits rabbit pyloric smooth muscle through neuronal motilin receptors.

BACKGROUND & AIMS: Erythromycin's effect in accelerating gastric emptying is attributed primarily to increased antral contractility. The aim of this study was to characterize erythromycin's effect on pyloric muscle. METHODS: Rabbit pyloric muscle strips were studied in vitro. RESULTS: Pyloric muscle strips developed spontaneous phasic contractions with a frequency of 1.9 +/- 0.1 contractions per minute. Erythromycin and motilin had dose-dependent inhibitory effects on pyloric muscle. At the maximal effective dose (50 mumol/L), erythromycin caused cessation of spontaneous contractions for 1.8 +/- 0.2 minutes, decreasing the initial 2-minute motility index to 35% +/- 9% (P < 0.01) of basal. In the presence of tetrodotoxin, both erythromycin and motilin increased pyloric contractility. Motilin tachyphylaxis both in the presence or absence of tetrodotoxin abolished the effects of erythromycin. The inhibitory effect of erythromycin was decreased by NG-nitro-L-arginine methyl ester and the vasoactive intestinal peptide antagonist [4-Chloro-D-Phe6, Leu17]vasoactive intestinal peptide. CONCLUSIONS: These studies suggest that motilin receptors are present on both pyloric muscle and inhibitory neurons to pyloric muscle, that the primary effect of erythromycin on the pylorus is mediated by activating motilin receptors on inhibitory motor neurons, and that both nitric oxide and vasoactive intestinal peptide may mediate the inhibitory effect of erythromycin.

Animals↗