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 37 records · Page 2Linked to original sources
PubMed1978

The development of tachyphylaxis to electrical stimulation in guinea-pig ileal longitudinal muscles and the possible participation of adenosine and adenine nucleotides.

1 Electrically (30 Hz) induced contractions of guinea-pig isolated ileal longitudinal muscles were reduced by tetrodotoxin (1 micron), adenosine (30 micron) and morphine (10 micron). 2 When stimulated with 10 or 30 Hz for 10 s at 1 min intervals, a progressive decline of amplitude of the contraction was seen (development of tachyphylaxis). At this time, the contractile response to 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP) (10 micron) was also greatly reduced. 3 The smaller responses to electrical stimulation and DMPP during tachyphylaxis were restored to their initial amplitude by the addition of theophylline (10 micron). The appearance of tachyphylaxis was prevented by pretreatment with theophylline (1 to 10 micron) and was greatly accelerated by pretreatment with dipyridamole (0.1 1 micron). 4 In [14C]-choline or [3H]-adenosine preloaded muscle strips, electrical stimulation (30 Hz) increased the 14C- or 3H-output, the effect being sensitive to tetrodotoxin blockade. The tachyphylaxis to electrical stimulation was accompanied by a considerable and sustained increase in 3H-output, an effect that was accelerated by dipyridamole (1 micron). The 14C-output initially increased but fell off gradually with the development of tachyphylaxis at which time theophylline (30 micron) reversed the fall. 5 There was a marked increase in the proportion of released [3H]-adenosine to its derivatives during the development of tachyphylaxis. Approximately 60% of the released total radioactivity after tachyphylaxis was found to be [3H]-adenosine. 6 These results suggest that the development of tachyphylaxis may be closely associated with the release of endogenous adenosine derivatives (mostly adenosine) which have presynaptic inhibitory actions on the cholinergic elements in guinea-pig ileum.

Acetylcholine↗
PubMed1977

The effects of somatostatin and metiamide on tachyphylaxis of pentagastrin stimulated gastric acid and pepsin secretion in the conscious cat.

1. Pentagastrin stimulated gastric acid and pepsin secretions show parallel rates of tachyphylaxis in the conscious cat. The responses to histamine show only slight tachyphylaxis. 2. Somatostatin 10 microng.kg(-1).hr(-1) inhibits pentagastrin but not histamine stimulated acid secretion and inhibits pentagastrin stimulated pepsin secretion. 3. The inhibition of pentagastrin stimulated acid and pepsin secretion by Somatostatin delays the tachyphylaxis of these responses, but the rates of tachyphylaxis when they do subsequently occur are identical. 4. Metiamide 10 mg-kg(-1)-hr(-1) equally inhibits histamine and pentagastrin stimulated acid secretion but does not inhibit pentagastrin stimulated pepsin secretion. 5. Inhibiton of acid secretion during metiamide infusion neither prevents nor delays acid nor pepsin tachyphylaxis. 6. It is suggested that tachyphylaxis of acid and pepsin secretion is a gastrin receptor phenomenon and that Somatostatin occupies or modifies the behaviour of these receptors, preventing tachyphylaxis. Metiamide, however, exerts its action only on the histmine H2-receptor and not the gastrin receptor mechanism, and this apparently does not prevent or delay acid tachyphylaxis.

Animals↗
PubMedDate not supplied

Angiotensin I, II, and II tachyphylaxis in the mesenteric vascular circuit of the rat.

Angiotensin tachyphylaxis is rapidly induced in the mesenteric vascular circuit of the rat perfused with a saline solution. there is crossed tachyphylaxis among angiotensins (AI, AII, and AIII). The angiotensin antagonist Sar 1-Ileu 8-AII is ineffective when the vascular preparation is previously rendered tachyphylactic to AII, showing that the AII receptors are not available during tachyphylaxis. This finding supports the theory that angiotensin tachyphylaxis is caused by receptor occupancy by the agonist. By perfusing the vascular preparation with aII solutions that were too diluted to produce vasoconstriction, tachyphylaxis to AII was induced. Therefore, AII receptors can be slowly saturated without producing vasoconstriction. The recoveries of the vasoconstrictor effect of AII and AIII at 30 and 60 minutes after tachyphylaxis are similar; thus, the dissociation constants of the AII- and AIII-receptor complexes should be alike. After three bolus injections of AI, the vascular preparation is completely refractory to AI, AII, and AIII. When the conversion of AI to AII is inhibited with captopril, AI no longer induces tachyphylaxis to AII and AIII. Thus, tachyphylaxis to AII and AIII induced by AI seems to be due not to the occupancy of AII receptors by AI but to the AII formation from AI "in situ."

Angiotensin I↗
PubMed1989

[Tachyphylaxis to local anesthetics].

Tachyphylaxis to local anesthetics is defined as decrease in duration, segmental spread, or intensity of a regional block after repeated doses of equal size, i.e. to maintain a given level of effect the dose has to be increased. In contrast, time-dependent variations in pain or circadian changes in the duration of local anesthetic action only simulate the occurrence of tachyphylaxis (pseudotachyphylaxis). Tachyphylaxis appears neither to be linked to structural (ester vs amide) or pharmacological properties of the local anesthetics (short- vs long-acting) nor to technique (surface anesthesia, conduction block, spinal, caudal, or epidural anesthesia, brachial plexus block) or mode of administration (intermittent vs continuous). There is even disagreement about the clinical significance of tachyphylaxis because some authors found it in almost every patient, others less often whereas a third group did not find tachyphylaxis at all. The mechanisms underlying tachyphylaxis are open to debate. Changes in pharmacokinetics (local alterations of disposition and absorption; decrease of perineural pH) and pharmacodynamics (antagonistic effects of nucleotides or increased sodium concentration; increase in afferent input) have been implicated. None of the theoretical considerations presented are strong enough to explain tachyphylaxis. However, results from isolated nerve preparations suggest that pharmacokinetics rather than pharmacodynamics might play a role in the development of tachyphylaxis.

Anesthetics, Local↗
PubMed1983

beta-Adrenergic tachyphylaxis in the rat and its reversal and prevention by ketotifen.

A strong, long-lasting and reproducible tachyphylaxis was produced in rats by implantation of osmotic minipumps delivering isoprenaline continuously. The degree of tachyphylaxis was determined by measuring the inhibitory effect of isoprenaline on the passive cutaneous anaphylaxis (PCA). One dose of ketotifen given 1 h before the PCA test reversed this in vivo tachyphylaxis, as did dexamethasone given 24 h earlier. Implantation of a second minipump containing ketotifen prevented the development of tachyphylaxis. Weak tachyphylaxis was induced in guinea-pig trachea in vitro by incubation with a high concentration of isoprenaline, the effect being estimated by measuring the relaxation of carbachol-contracted trachea. Ketotifen partially restored the sensitivity of the trachea but this was considered to be a direct potentiation of isoprenaline effects rather than a reversal of tachyphylaxis since the same effect was seen in non-pretreated trachea. It is thought that the reversal of experimental beta-adrenergic tachyphylaxis by ketotifen could have implications for its use in the prophylactic treatment of asthma.

Adrenergic beta-Agonists↗
PubMed1989

Effect of halothane concentration on tachyphylaxis to sodium nitroprusside.

The relationship between halothane concentration and tachyphylaxis to sodium nitroprusside (SNP) was studied in a rabbit model. Three groups of six rabbits (groups A, B, and C) were anesthetized with halothane at 0.75, 1.0, and 1.25 vol% end-tidal, respectively. SNP-induced hypotension was maintained for 135 min or until a cumulative total dose of 12 mg/kg had been infused (defined as "marked tachyphylaxis"). Plasma norepinephrine (NE), epinephrine (EPI) levels, and plasma renin activity (PRA) were measured. Initial mean arterial pressure (MAP) (72 +/- 2 mm Hg), heart rate (325 +/- 12 beats/min), and the amount of SNP required to induce 40% hypotension (19 +/- 4 micrograms/kg/min) did not differ significantly among the three groups. In group A, five out of six animals exhibited "marked tachyphylaxis." In group B, only one animal showed "marked tachyphylaxis"; the remaining five required a dose rate of 104 +/- 38 micrograms/kg/min at 135 min to maintain a 40% reduction in MAP. In group C, none of the animals showed "marked tachyphylaxis"; the dose rate of SNP required after 135 min was 29 +/- 14 micrograms/kg/min. In all groups, SNP dose rate was found to best correlate (p less than 0.0005, r = 0.79) with NE levels and not with PRA or arterial blood pH. This implies that reflex sympathetic activation is the measured mediator of SNP tachyphylaxis. Halothane blunted the tachyphylaxis (sympathetic response) to SNP-induced hypotension at higher concentrations.

Animals↗
PubMed1992

Tachyphylaxis of the intrinsic cardiac nerves to nicotine: effects on A-V nodal conduction.

1. The possibility that responses of the intrinsic cardiac nerves (ICN) of the dog to nicotinic stimulation are influenced by tachyphylaxis to repeated administration of nicotine (NIC) was evaluated in an anaesthetized preparation. Prolongation of A-V conduction was used as an index of ICN responsiveness. 2. Twenty dogs were placed on cardiopulmonary bypass and an electrode was sutured over the His bundle. Both vagi were sectioned, beta-adrenoceptor blockade instituted, and the hearts were paced. Nicotine (2-100 micrograms) was administered directly into the coronary circulation via an aortic catheter. Tachyphylaxis was estimated from the rate of deterioration of negative dromotropic effect of NIC in response to various protocols of repeated doses. 3. Tachyphylaxis was not observed in response to repeated doses of acetylcholine. 4. Tachyphylaxis to nicotine was found to be both time- and dose-dependent; i.e. increasing the dose or decreasing the time between doses to less than 3 min augmented its development. 5. Tachyphylaxis was pronounced after 5 x 100 micrograms doses of NIC, even if the test doses were greater than 3 min apart and 20 min was allowed to elapse between the two series of test doses. 6. These data are descriptive in nature and no mechanism for the tachyphylaxis could be deduced. Pharmacokinetic data of this nature have not been previously reported for nicotinic stimulation of the intrinsic parasympathetic ganglia of the canine heart. Tachyphylaxis can be avoided when testing the intrinsic innervation of the canine heart if the doses used are less than 100 micrograms and are administered at least 3 min apart.

Acetylcholine↗
PubMed1988

Characteristics of tachyphylaxis to inhaled histamine in anesthetized dogs.

Three consecutive dose-response curves to aerosolized histamine were obtained in 11 anesthetized dogs. All dogs showed desensitization (i.e., tachyphylaxis) to high doses of histamine. Tachyphylaxis was highly reproducible. No tachyphylaxis occurred with inhaled acetylcholine or methacholine. Beta-Adrenergic blockade with propranolol or muscarinic blockade with atropine given intravenously had no effect on the histamine tachyphylaxis. Duration of thiamylal anesthesia did not alter the histamine responsiveness. Histamine tachyphylaxis was also seen with chloralose-urethan anesthesia. Since tachyphylaxis is not observed with acetylcholine, it cannot be attributed to a general decline in muscle contractility. We conclude that histamine tachyphylaxis in vivo is not explained by effects of cholinergic reflexes, catecholamine release, duration of anesthesia, or, probably, type of anesthetic agent.

Acetylcholine↗
PubMed1990

Tachyphylaxis to inhaled methacholine in normal but not asthmatic subjects.

Methacholine inhalation tests measure airway responsiveness in asthmatic and normal subjects. Tachyphylaxis occurs with repeated methacholine inhalations in normal subjects. The purpose of this study was to examine the time course and mechanisms of methacholine tachyphylaxis in normal subjects and to determine whether this occurs in mildly asthmatic subjects. Fifteen normal and nine asthmatic subjects were studied on 2 study days, at least 48 h apart. Each day, two inhalation tests were carried out. On one day, subjects performed two methacholine inhalation tests 3 h later by a methacholine test. Results were expressed as the provocation concentration causing a 20% fall in forced expiratory volume in 1 s (FEV1), (PC20). All normal subjects developed methacholine tachyphylaxis. The mean PC20 increased from 47.3 mg/ml (%SE 1.34) to 115.6 (%SE 1.51) (P less than 0.0001) in a 3-h interval. This increase lasted for greater than or equal to 6 h (P = 0.012). Asthmatic subjects did not develop methacholine tachyphylaxis. Their mean methacholine PC20s were 1.6 mg/ml (%SE 1.4) and 1.5 (%SE 1.4) (P = 0.75) 3 h later. In two other series of experiments, normal subjects were pretreated with the cyclooxygenase inhibitors indomethacin (100 mg/day) or flurbiprofen (150 mg/day) or a placebo for 3 days before two methacholine tests 3 h apart. Both indomethacin and flurbiprofen significantly inhibited the development of methacholine tachyphylaxis. These results confirm that methacholine tachyphylaxis occurs in normal subjects, lasts greater than or equal to 6 h, and may occur through the release of inhibitory prostaglandins. By contrast, methacholine tachyphylaxis does not occur in asthmatic subjects.

Administration, Inhalation↗
PubMedDate not supplied

Effect of age and spontaneous hypertension on the tachyphylaxis to 5-hydroxytryptamine and angiotensin II in the isolated rat kidney.

The isolated and perfused kidney of the mature spontaneously hypertensive rat (SHR) exhibits an increased vascular reactivity and a delayed tachyphylaxis to 5-hydroxytryptamine, when compared to weight-matched normotensive animals. To evaluate the influence of the duration of the hypertensive state on these differences, the vascular reactivity to 5-hydroxytryptamine was determined in isolated kidneys from age-matched normotensive and spontaneously hypertensive rats of 3.5, 6 and 12 months of age. Responses to increasing doses of 5-hydroxytryptamine were compared. At all ages the responses to the agonist were greater in the SHR than in the control rats. In the normotensive rats, the sensitivity to the monoamine decreased, while the maximal response increased with aging. The vascular reactivity to increasing doses of 5-hydroxytryptamine was not altered by aging in the SHR. There was a significant correlation between the maximal vasoconstrictor response to 5-hydroxytryptamine in the isolated kidneys and the systolic arterial blood pressure (SBP) of the donor rats. Maximal constrictor responses to 5-hydroxytryptamine were repeated at given intervals. The degree of tachyphylaxis was decreased in hypertensive rats compared with normotensive rats at 3.5, and 6 months age. Tachyphylaxis to 5-hydroxytryptamine was depressed by aging in both normotensive and hypertensive rats. By contrast, tachyphylaxis to angiotensin II (AII) was not effected by either age or hypertension. There was no cross-tachyphylaxis between 5-hydroxytryptamine and AII. Lowering the Ca2+-concentration of the perfusate did not affect tachyphylaxis to either 5-hydroxytryptamine or AII. The present experiments indicate that the delayed tachyphylaxis to 5-hydroxytryptamine in the kidneys of SHR is due to a specific alteration of th vascular smooth muscle cells, which may be the consequence of premature aging.

Aging↗
PubMed1992

Regional variation in acute vascular homologous tachyphylaxis.

The development of tachyphylaxis or desensitization in a tissue upon repeated application of an agonist is a well-established phenomenon. To investigate the possible basis of vascular homologous tachyphylaxis, vasomotor responses in isolated cerebral and peripheral blood vessels from the cat, dog and rabbit upon repeated application of several agonists were examined using in vitro tissue bath techniques. Tachyphylaxis to vasodilator responses developed to repeated application of vasoactive intestinal polypeptide (VIP) but not to beta adrenergic agonist, forskolin, 8-bromo-cyclic AMP, sodium nitroprusside or 8-bromo-cyclic GMP in feline cerebral arteries. The tachyphylaxis to VIP-induced responses varied among regions and was greatest in the internal carotid artery (ICA), followed by the middle cerebral artery and least in the basilar artery (BA). Cerebral arteries also developed significant tachyphylaxis to constriction induced by repeated applications of neuropeptide Y (NPY), alpha-1 adrenergic agonist, but not to alpha-2 adrenergic agonist, acetylcholine (ACh) or KCl. The tachyphylaxis to constrictions induced by repeated application of neuropeptide Y (NPY) also varied among regions, but was different from that induced by VIP; it was greatest in the BA, followed by the middle cerebral artery and least in the ICA. Similar results were obtained in arteries without endothelial cells. The density of regional innervation of NPY-immunoreactive fibers, which is densest in ICA and sparsest in BA, parallels that of VIP-immunoreactive fibers in these three regions. There is no positive correlation between density of catecholamine fluorescence fibers and degree of tachyphylaxis to noradrenaline-induced constriction in cat ICA, dog saphenous arteries and rabbit ear arteries either.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1984

Development of histamine tachyphylaxis in the guinea-pig mesenteric artery.

Histamine, norepinephrine and KCl each evoke contractile responses in isolated guinea-pig mesenteric artery. However, only the contractile response to histamine was characterized by acute desensitization or tachyphylaxis. The tachyphylaxis observed to histamine was independent of the time interval between successive administrations up to at least 1 hr. The histamine H1-receptor blocker, chlorpheniramine (10(-9) M), completely inhibited contractile responses to histamine (10(-5) M). In contrast, metiamide (10(-4) M), an H2-receptor blocker, potentiated contractions which were characterized by tachyphylaxis. Propranolol (10(-6) M), phentolamine (10(-6) M) and atropine (10(-6) M) affected neither the contractile response itself nor the tachyphylaxis to histamine (10(-5) M). Indomethacin (10(-5) M) and aspirin (3 X 10(-4) M) potentiated the initial contraction induced by histamine (10(-5) M) and completely abolished the tachyphylaxis. The response to the initial application of histamine (10(-5) M) was not affected by the reduction of [Ca++] to 0.25 mM or by diltiazem (10(-5) M) or verapamil (10(-5) M). The tachyphylaxis to histamine was, however, suppressed slightly but significantly by the reduction of [Ca++]o and by Ca++ antagonists. These results suggest that the development of tachyphylaxis to histamine in the isolated guinea-pig mesenteric artery may result from the production of prostaglandins which are sensitive to Ca++.

Animals↗
PubMed1995

Angiotensin II tachyphylaxis in the guinea pig ileum and its prevention: a pharmacological and biochemical study.

Angiotensin II (AII) tachyphylaxis occurs in the guinea pig ileum, but is not induced by analogs lacking the N-terminal amino group or the Arg2 guanidino group. Both AII and Lys2AII increased cell inositol trisphoshate content in cultured intestinal smooth muscle cells. Protein kinase C inhibition by staurosporine or downregulation by prolonged incubation with phorbol reverted tachyphylaxis of the inositol trisphoshate response, but not that of the Na+ uptake response, indicating that the uncoupling of the phosphoinositide signal system by protein kinase C did not involve all processes distal to receptor activation. Tachyphylaxis of the Na+ uptake response was prevented when receptor internalization was blocked by reduction of the temperature (4 degrees C) or by pretreatment of the cells with phenylarsine oxide. Acid washings, which prevented tachyphylaxis of the 24Na+ influx response, also prevented tachyphylaxis of the contractile response of the guinea pig ileum to AII. Although these findings suggest that sequestration or internalization of the AII receptor might be involved in AII tachyphylaxis, binding of [125I]AII and of [125I]Lys2AII to the cells was equally unaffected by repeated administrations of the peptides. The results suggest that conformational change of the AII-receptor complex within the plasma membrane, but not internalization, is the most important factor responsible for tachyphylaxis.

Alkaloids↗
PubMed1996

Tachyphylaxis to angiotensin II and [Phe4]-angiotensin II in the rat mesentery in vivo.

The existence of tachyphylaxis to angiotensin II (Ang II) in vivo is not unequivocally established, and the hydroxyl group of the Tyr4 residue of Ang II has been suggested as a determinant of tachyphylaxis. In view of these observations, we conducted a series of experiments to assess and compare the ability of Ang II and [Phe4]-Ang II to induce tachyphylaxis in vivo. All experiments were performed in the autoperfused rat mesenteric vascular bed. The tachyphylaxis to intramesenteric (IMA) infusions of Ang II was minimal, and after 120 min of continuous infusion (33 pmol/min), Ang II retained most of its vasoconstrictor activity (67.7 +/- 6.6% of the initial response). Also most of the agonist activity was retained even when Ang II was administered continuously in a dose-increasing manner (1-33 pmol/min). Continuous IMA infusions of single doses of [Phe4]-Ang II caused an initial full response that rapidly declined, and after 120 min retained only 18.2 +/- 9.2% of the initial response. Single continuous IMA infusion of [Phe4]-Ang II induced greater vasoconstrictor responses compared with vascular responses to the same doses delivered after the infusion of smaller doses. This difference was significant (P < .001, unpaired Student's t test) for all doses (10, 100, 330 and 1000 pmol/min) of [Phe4]-Ang II. In conclusion, although the development of tachyphylaxis to Ang II in vivo is minimal, tachyphylaxis to [Phe4]-Ang II does occur (at least in rat mesenteric vascular bed). Thus, omission of the hydroxyl group in position 4 dramatically increases the tachyphylactic potential, while preserving full agonist activity. These results suggest that the hydroxyl group of Tyr4 may protect the Ang II receptor from changes that induce tachyphylaxis.

Angiotensin II↗
PubMed1988

Tachyphylaxis of dipsogenic activity to intracerebroventricular administration of angiotensins.

Repeated intracerebroventricular (i.c.v.) administration of angiotensin II (AII) and angiotensin III (AIII) induced dipsogenic tachyphylaxis in the Sprague-Dawley rat. AIII caused a rapid suppression of drinking, whereas AII showed a progressive decline of water consumption with repeated injections. Tachyphylaxis due to the repeated i.c.v. application of AII failed to abolish subsequent drinking induced by neurotensin or carbachol, suggesting that the tachyphylaxis may be specific to the angiotensinergic system. However, AII-induced tachyphylaxis caused a complete elimination of bestatin-induced drinking which was anticipated given the likelihood that this aminopeptidase B inhibitor has its dipsogenic effect by inhibiting degradation of endogenous angiotensins. Angiotensin-induced tachyphylaxis responses could not be attributed to diminished dipsogenic activity due to volemic expansion of either the cerebroventricular space or gastrointestinal tract. These results concerned with central tachyphylaxis are consistent with previous findings in the periphery and suggest that desensitization of angiotensin receptors occurs in both populations.

Angiotensin II↗
PubMed1983

Role of the two N-terminal residues of angiotensin II in the production of tachyphylaxis.

The structural requirements for the production of angiotensin tachyphylaxis in the guinea-pig ileum were studied by analyzing the tachyphylactic properties of the following synthetic analogues of angiotensin II (AII): [1-sarcosine]AII, [1-betaine]AII; [1-guanidinoacetic]AII; betainyl-AII; [2-lysine]AII; [2-ornithine]AII. In the non-atropinized ileum, no tachyphylaxis was observed with any of the following analogues: [2-lysine]AII, [2-ornithine]AII, [2-ornithine]AII, [1-betaine]AII and betainyl-AII. [1-Guanidinoacetic]AII induced tachyphylaxis, but to a smaller degree than AII, while [1-sarcosine]AII was significantly more tachyphylactic than AII. Similar results were obtained in the atropinized ileum, except that moderate tachyphylaxis was also observed with betainyl-AII and [1-betaine]AII. The analogues with lysine or ornithine residues in position 2 did not induce tachyphylaxis under any of the conditions studied. It is concluded that, besides the protonated N-terminal amino group, the guanidino group of the Arg2 side-chain is essential for the manifestation of angiotensin tachyphylaxis in the guinea-pig ileum.

Amino Acid Sequence↗
PubMed2005

Tachyphylaxis to beta2-agonists in Spanish asthmatic patients could be modulated by beta2-adrenoceptor gene polymorphisms.

BACKGROUND: The study of determinants of asthma is a subject of much interest currently, especially the pharmacogenetic aspects of asthma management. Genetic polymorphisms affecting amino-acids at positions 16 and 27 within beta(2)-adrenoceptor (beta(2)AR) gene have been implicated in the asthma phenotypes and influence on the variability observed in response to use of bronchodilator agents used in the treatment of asthma. Whether these polymorphisms alter the bronchoprotection response to beta(2)-agonist treatment in Spanish asthmatic population is unknown. The aim of this study was to investigate whether genetic polymorphisms within beta(2)AR gene modulate the clinical outcomes of the individual response to beta(2)-agonist therapy and the development of desensitization in Spanish asthmatic patients. METHODS: In a prospective, case-control study were included 80 asthmatic patients. Based on the standard criteria, patients were classified into two groups: patients with tachyphylaxis and good responders to beta(2)-agonist therapy. DNA samples were genotyped for the Arg(16)Gly and Glu(27)Gln alleles within the beta(2)AR gene as well as in 64 control samples from blood donors. RESULTS: Arg(16) allele was slightly more frequent within the group with tachyphylaxis (P=0.039), whereas Gly(16) allele carriers were overrepresented within the group of good responders (59.7%, P=0.028). On the other hand, the allele frequency of Gln(27) and the proportion of Gln(27) carriers was higher within the group with tachyphylaxis (P=0.010 and 0.049, respectively) and Glu(27) allele carriers were overrepresented within the group of good responders (P=0.026). The Arg(16) and Gln(27) alleles were in strong linkage disequilibrium across this locus, resulting in the occurrence of disease haplotype. CONCLUSIONS: The predisposition to develop tachyphylaxis in our population seems to be linked to the Arg(16) and Gln(27) alleles and to the Arg(16)/Gln(27) risk haplotype (positive association between the presence of the Arg(16) and Gln(27) alleles and tachyphylaxis). The Arg(16) allele is perhaps overrepresented due to the strong linkage disequilibrium between both polymorphisms. The presence of the Glu(27) allele seems to be a protective factor against tachyphylaxis in this cohort study.

Adolescent↗
PubMed1993

Tachyphylaxis in cardiovascular responses to cocaine in conscious rats.

Tachyphylaxis has been shown to occur in human cardiovascular responses to cocaine. The present study was designed to establish a response curve for cardiovascular parameters in conscious, chronically instrumented rats and to investigate the degree of tachyphylaxis occurring in these parameters after repeated doses of cocaine. Cardiovascular parameters evaluated included arterial pressure, heart rate (HR), and electrocardiogram (ECG). Administration of low doses (0.0625 mg/kg) of cocaine caused significant increases in arterial pressure. Changes in HR accompanying intravenous (i.v.) cocaine were usually biphasic, characterized by an initial reflex bradycardia, followed by a secondary tachycardia lasting several minutes. Tachyphylaxis was observed in the cardiovascular responses when cocaine was administered repetitively at 5-min intervals. This tachyphylaxis was not apparent when the interval between cocaine infusions was extended to 2 h. The mechanism responsible for the tachyphylaxis is hypothesized to be mediated by the presynaptic alpha 2-receptors. Conscious animals were very sensitive to i.v. cocaine administration, and tachyphylaxis to repeated cocaine administration was observed. Both observations must be considered when interpreting cardiovascular studies using cocaine.

Adrenergic alpha-Antagonists↗