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 631 records · Page 35Linked to original sources
PubMed1967

Responses of skin blood vessels to bradykinin, histamine and 5-hydroxytryptamine.

1. The responses of human cutaneous blood vessels to intradermal injection of bradykinin, histamine and 5-hydroxytryptamine (serotonin) are studied in order to evaluate the ability of these agents to mediate the vascular changes of sustained acute inflammation in the skin.2. Bradykinin produces erythema, owing to a direct effect on blood vessels, and wealing. Dose-response studies indicate that bradykinin is more potent than serotonin or histamine in respect of wealing.3. The response to serotonin differs qualitatively as well as quantitatively according to dose. High doses cause wealing and erythema with the characteristics of an axon reflex flare, but low doses produce erythema by a local effect without wealing.4. Using the technique of arterial occlusion, the occurrence of tachyphylaxis in respect of wealing was demonstrated with histamine and serotonin, but not with bradykinin. This evidence suggests that of the three agents, only bradykinin can mediate increased vascular permeability in sustained acute inflammation.5. The specificity of tachyphylaxis and the failure of anti-histamine to antagonize bradykinin wealing suggest that bradykinin and histamine act on separate blood vessel receptors.6. Corticosteroids do not inhibit wealing due to a wide range of doses of bradykinin. The anti-inflammatory activity of corticosteroids may therefore be due to reduced formation of kinins.

Adult↗
PubMed1994

Inhibitory effect of adenosine on electrical activity of frog melanotrophs mediated through A1 purinergic receptors.

1. The effects of adenosine were studied in cultured frog melanotrophs by the patch-clamp technique. 2. In cell-attached experiments, most cells responded to adenosine (50 microM) by a reversible inhibition of action current discharges without any apparent desensitization. 3. In whole-cell experiments, adenosine provoked a hyperpolarization accompanied by a depression of spontaneous action potentials and a decrease in membrane resistance. When adenosine was repeatedly applied, tachyphylaxis was observed. Addition of GTP (100 microM) in the intracellular solution augmented the percentage of cells hyperpolarized by adenosine, and the duration and amplitude of the hyperpolarization, and prevented the tachyphylaxis. 4. Pretreatment with pertussis toxin (1 microgram ml-1) blocked adenosine-induced inhibition. 5. In cells dialysed with the non-hydrolysable GTP analogue GTP gamma S (100 microM), adenosine caused a sustained, strong hyperpolarization and an irreversible inhibition of spikes. 6. The effect of adenosine was mimicked by the A1 receptor agonist R-PIA (R-N6-phenylisopropyl-adenosine; 50 microM) and blocked by the A1 receptor antagonist CPDPX (8-cyclopentyl-1,3-dipropylxanthine, 50 microM). The A2 receptor antagonist CGS15943 (9-chloro-2-(2-furanyl)-5,6-dihydro-1,2,4-triazolo[1,5-c] quinazoline-5-imine; 50 microM) did not affect the adenosine-induced response. 7. The results suggest that, in frog melanotrophs, adenosine exerts a direct hyperpolarizing effect accompanied by blockage of spontaneous action potentials. The effect of adenosine is mediated through A1 receptors coupled to a Gi/o protein.

Action Potentials↗
PubMed1992

Inhibitory and excitatory mechanisms of neurotensin action in canine intestinal circular muscle in vitro.

The effect of neurotensin on canine ileal circular muscle devoid of myenteric plexus was investigated using single and double sucrose gap techniques. Similar results were obtained with microelectrode techniques. Neurotensin caused a temperature-sensitive and dose-dependent biphasic response, an initial hyperpolarization associated with inhibition of contractile activity, followed by an excitatory phase, usually consisting of spike discharge and tonic and phasic contractions, for which depolarization was not required. Neither response was affected by tetrodotoxin, phentolamine, propranolol, or atropine. The hyperpolarization was associated with decreased membrane resistance, blocked by 10(-7) M apamin, and converted to tonic depolarization by apamin (10(-6) M). Tachyphylaxis to neurotensin occurred when the stimulation interval was less than 20 min. After Ca2+ depletion, depolarization was observed instead of the hyperpolarization; this depolarization was not affected by nitrendipine and was gradually abolished with repetitive stimulation at 20-min intervals. When Ca2+ was present, nifedipine did not alter the hyperpolarizing phase of the response but inhibited spiking and blocked all contractions. The excitatory phase of the response was enhanced by Bay K-8644. Neuromedin N elicited a response identical with that of neurotensin. The responses of the two peptides were completely cross tachyphylactic. Inhibitory junction potentials were not affected by neurotensin tachyphylaxis. It is concluded that neurotensin and neuromedin N activate apamin-sensitive, calcium-dependent potassium channels in circular muscle, causing membrane hyperpolarization and inhibition of muscle contraction. Release of intracellular calcium is involved in the activation of these potassium channels.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1998

Involvement of pituitary adenylate cyclase-activating peptide in opossum internal anal sphincter relaxation.

Despite its widespread distribution and significance in the gut, the role of pituitary adenylate cyclase-activating peptide (PACAP) in internal anal sphincter (IAS) relaxation has not been examined. This study examined the role of PACAP in nonadrenergic noncholinergic (NANC) nerve-mediated relaxation of IAS smooth muscle. Circular smooth muscle strips from the opossum IAS were prepared for measurement of isometric tension. The influence of PACAP and vasoactive intestinal peptide (VIP) antagonists and tachyphylaxis on the neurally mediated IAS relaxation was examined either separately or in combination. The release of these neuropeptides in response to NANC nerve stimulation before and after the nitric oxide (NO) synthase inhibitor Nomega-nitro-L-arginine and NO was also investigated. Both PACAP and VIP antagonists caused significant attenuation of IAS relaxation by NANC nerve stimulation. The combination of the antagonists, however, did not have an additive effect on IAS relaxation. VIP tachyphylaxis caused significant suppression of IAS relaxation by NANC nerve stimulation. PACAP and VIP were found to be released by NANC nerve stimulation and exogenous NO. The data suggest the involvement of PACAP in IAS relaxation primarily by the activation of PACAP1/VIP receptor and lack of its independent role in the relaxation. Furthermore, NO may regulate the presynaptic release of PACAP and VIP.

Anal Canal↗
PubMed1986

Interaction of bradykinin and prostaglandin E1 on cardiac pressor reflex and sympathetic afferents.

Bradykinin applied to the epicardium stimulates cardiac sympathetic afferents and evokes a reflex increase in arterial blood pressure. In anesthetized cats we examined the potentiation of these effects by prostaglandin E1 (PGE1) applied to the ventricular epicardium. We recorded cardiac afferent impulses from the second to the fifth left thoracic sympathetic rami. PGE1 (0.1 microgram/ml) alone had little effect on blood pressure, but it significantly increased the pressor response to bradykinin, and it reduced or abolished tachyphylaxis to repeated applications of bradykinin. Both mechanosensitive and chemosensitive sympathetic cardiac afferents were stimulated by bradykinin. Indomethacin (intravenous) caused a small reduction in the afferent response to bradykinin. Epicardial application of PGE1 significantly increased the response (magnitude and duration) of chemosensitive endings to bradykinin but not that of mechanosensitive endings; however, PGE1 abolished the tachyphylaxis of both chemosensitive and mechanosensitive endings to repeated applications of bradykinin. Because both bradykinin and prostaglandins are released in the ischemic myocardium, their interactive effect on cardiac sympathetic afferents could play a part in the sensory and reflex responses to myocardial ischemia.

Action Potentials↗
PubMed1988

Role of platelets in contraction of canine tracheal muscle elicited by PAF in vitro.

To elucidate mechanisms of platelet-activating factor (PAF)-induced contraction, we studied the effect of PAF on 203 canine tracheal smooth muscle (TSM) strips from 45 dogs in vitro in the presence and absence of platelets. PAF (10(-11) to 10(-7) M) alone caused no contraction of TSM even in the presence of airway epithelium. In the presence of 2 x 10(5) platelets/microliter, PAF was an extremely potent contractile agonist (threshold 10(-11) M). This response was inhibited by the PAF antagonist, CV-3988 (10(-6) M), and reversed by the serotonin antagonist, methysergide (EC50 = 3.7 +/- 0.79 x 10(-9) M). Neither atropine nor chlorpheniramine (10(-9) to 10(-6) M) attenuated the response to PAF + platelets. In the presence of platelets, 10(-7) M PAF caused an increase in perfusate concentration of serotonin from 0.93 +/- 0.037 x 10(-8) to 1.7 +/- 0.046 x 10(-8) M (P less than 0.001). Tachyphylaxis, previously demonstrated to be irreversible, was shown to be a platelet-dependent phenomenon; contraction could be repeated in the same TSM after addition of fresh platelets. We demonstrate that PAF-induced contraction of canine TSM is caused by the release of cellular intermediates such as serotonin from platelets. We also demonstrate the site of PAF-induced tachyphylaxis in airway smooth muscle contraction.

Animals↗
PubMed1975

Inhibition of immediate hypersensitivity reactions in the rat by ICI 74,917 and disodium cromoglycate.

ICI 74,917, a potent inhibitor of IgE-mediated passive cutaneous anaphylaxis (PCA) in the rat, exhibited tachyphylaxis in that pre-dosing sensitised rats with a high dose of compound reduced the inhibitory effect on rat PCA of a second dose given at challenge. This phenomenon was most apparent when the pre-dose-challenge dose interval was 15--60 min. Similar findings were obtained using antigen-induced histamine release in vitro from rat peritoneal cells. In these respects, ICI 74,917 was similar to disodium cromoglycate (DSCG) although DSCG appeared less effective in inducing tachyphylaxis than ICI 74,917. There was no evidence in vivo or in vitro that a high dose of either DSCG or ICI 74,917 enhanced the activity of a second low dose of either drug given at challenge.

Animals↗
PubMed1983

RHC 3024: antiallergic activity in vitro and comparison with disodium cromoglycate and other antiallergic agents.

RHC 3024 has been investigated for its antiallergic activity in three in vitro models of anaphylaxis. We have also compared its activity profile in these models with that of disodium cromoglycate (DSCG) and other antiallergic agents. As an inhibitor of antigen-induced release of histamine from rat mast cells RHC 3024 was 4 times more potent than DSCG. In the same model the activity profile of RHC 3024 was identical to that of DSCG in the following respects: loss of inhibitory activity with increasing preincubation time, reversibility of the inhibition, tachyphylaxis and cross-tachyphylaxis to each other and inability to inhibit histamine release stimulated by Ca++ ionophore, dextran/phosphatidyl serine and compound 48/80. Both drugs had no effect in the other two models, IgG1-mediated histamine release from guinea pig lung and anti-IgE-induced histamine release from human basophils. We conclude: (1) RHC 3024 is a potent inhibitor of mediator release with a mechanism of action similar to that of DSCG, M&B 22,948, PRD-92-Ea and AH-7725 and (2) the in vitro activity profiles of proxicromil, doxantrazole, ICI 74,917 and WY-16,922 are different from DSCG and RHC 3024.

Animals↗
PubMed1996

Extracellular guanosine 3',5'-cyclic monophosphate and disodium cromoglycate share a similar spectrum of activity in the inhibition of histamine release from isolated mast cells and basophils.

In comparison to adenosine 3',5'-cyclic monophosphate (cAMP), surprisingly little is known regarding the role of guanosine 3',5'-cyclic monophosphate (cGMP) in the functional modulation of mast cells and basophils. In the present study, the ability of cGMP, cAMP, and a range of related compounds, to inhibit immunologically induced histamine release from these cells was investigated and compared to the anti-asthmatic drug disodium cromoglycate (DSCG). Exogenously applied cGMP produced a potent inhibition of histamine release from rat peritoneal mast cells, but cAMP had a negligible effect. The attenuation noted with cGMP was markedly reduced if cells were pretreated with the nucleotide before stimulation. Similar results were obtained with DSCG. The inhibitory and tachyphylactic effects noted with cGMP were mimicked by direct derivatives of the compound but not by a range of other cyclic or guanosine nucleotides. The time courses of the induced tachyphylaxis seen with cGMP and DSCG were similar, and cross-tachyphylaxis between the two compounds was observed. In addition, both cGMP and DSCG showed a comparable spectrum of activity against mast cells isolated from the mouse, guinea pig, and human. The parallel effects of the two agents suggests that they may inhibit mediator release from mast cells through similar mechanisms.

Animals↗
PubMed2006

Cardiac-specific ablation of G-protein receptor kinase 2 redefines its roles in heart development and beta-adrenergic signaling.

G-protein receptor kinase 2 (GRK2) is 1 of 7 mammalian GRKs that phosphorylate ligand-bound 7-transmembrane receptors, causing receptor uncoupling from G proteins and potentially activating non-G-protein signaling pathways. GRK2 is unique among members of the GRK family in that its genetic ablation causes embryonic lethality. Cardiac abnormalities in GRK2 null embryos implicated GRK2 in cardiac development but prevented studies of the knockout phenotype in adult hearts. Here, we created GRK2-loxP-targeted mice and used Cre recombination to generate germline and cardiac-specific GRK2 knockouts. GRK2 deletion in the preimplantation embryo with EIIa-Cre (germline null) resulted in developmental retardation and embryonic lethality between embryonic day 10.5 (E10.5) and E11.5. At E9.5, cardiac myocyte specification and cardiac looping were normal, but ventricular development was delayed. Cardiomyocyte-specific ablation of GRK2 in the embryo with Nkx2.5-driven Cre (cardiac-specific GRK2 knockout) produced viable mice with normal heart structure, function, and cardiac gene expression. Cardiac-specific GRK2 knockout mice exhibited enhanced inotropic sensitivity to the beta-adrenergic receptor agonist isoproterenol, with impairment of normal inotropic and lusitropic tachyphylaxis, and exhibited accelerated development of catecholamine toxicity with chronic isoproterenol treatment. These findings show that cardiomyocyte autonomous GRK2 is not essential for myocardial development after cardiac specification, suggesting that embryonic developmental abnormalities may be attributable to extracardiac effects of GRK2 ablation. In the adult heart, cardiac GRK2 is a major factor regulating inotropic and lusitropic tachyphylaxis to beta-adrenergic agonist, which likely contributes to its protective effects in catecholamine cardiomyopathy.

Adrenergic beta-Agonists↗
PubMed1990

Role of thromboxane A2 in the cardiovascular response to intracoronary C5a.

Intracoronary administration of complement component C5a induces transient decreases in coronary blood flow and regional left ventricular segment shortening, associated with intramyocardial granulocyte trapping. We evaluated the influence of a cyclooxygenase inhibitor (acetylsalicylic acid, n = 8) or a thromboxane A2/prostaglandin H2 receptor antagonist (SQ29548, n = 6) on these C5a-induced cardiovascular responses. Open-chest anesthetized pigs were instrumented to monitor heart rate, arterial blood pressure, left anterior descending coronary blood flow, regional left ventricular segment shortening, and dP/dt. Oxygen content, lactate concentration, leukocyte count, and thromboxane B2, the stable metabolite of thromboxane A2, were measured in arterial and regional coronary venous blood. Repetitive injections of intracoronary C5a (500 ng) given 60 minutes apart showed no tachyphylaxis of the hemodynamic response. However, tachyphylaxis was seen in coronary blood flow changes when injections were spaced 30 minutes apart. An increase in myocardial oxygen extraction and lactate production was observed after intracoronary C5a. Administration of acetylsalicylic acid (50 mg/kg i.v.) attenuated C5a-induced decreases in coronary blood flow (-8 +/- vs. -3 +/- 1 ml/min) and regional left ventricular segmental shortening (-10 +/- 3% vs. -2 +/- 1%) and blocked the maximal increase in coronary venous thromboxane B2 (2.0 +/- 0.1 vs. 0.2 +/- 0.1 pmol/ml plasma). Furthermore, SQ29548 (30 micrograms/kg/min) reduced C5a-induced changes in coronary blood flow (-13 +/- 2 vs. -4 +/- 2 ml/min) and segmental shortening (-14 +/- 2% vs. -3 +/- 1%). Neither cyclooxygenase inhibition nor thromboxane A2/prostaglandin H2 antagonism blocked the decrease in coronary venous granulocyte count.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1997

Effects of experimental rhinovirus 16 infection on airway hyperresponsiveness to bradykinin in asthmatic subjects in vivo.

Disturbance of the balance between excitatory and inhibitory activity of the airway sensory nerves has been implicated in asthma pathogenesis, particularly during exacerbations of the disease. The objective of this study was to examine the effect of experimental rhinovirus 16 (RV16) infection on airway responsiveness to bradykinin, a potent sensory nerve stimulus, in asthma. Thirteen atopic, mildly asthmatic subjects participated in a parallel, placebo-controlled study. A total dose of 2.6 to 5.6 x 10(4) TCID50 RV16 (n = 7) or its diluent (n = 6) was inoculated on 2 consecutive days (Days 0 and 1). Histamine and bradykinin challenges were performed before (Days-7 and-6) and after (Days 3 and 4) inoculation. The response was measured by FEV1 and partial flow-volume curves, and it was expressed as PC20FEV1 and PC40V40p, respectively (changes expressed in doubling dose: DD). Before inoculation, PC20FEV1 and PC40V40p to histamine were not significantly different between the groups (p > or = 0.22), whereas PC20FEV1 and PC40V40p to bradykinin tended to be higher in the RV16 group (p = 0.11 and p = 0.06, respectively). PC20FEV1 and PC40V40p to histamine decreased significantly in the RV16 group (mean change +/- SEM: -0.65 +/- 0.20 DD, p = 0.02 and -0.98 +/- 0.28 DD, p = 0.01, respectively), but not in the placebo group (p > or = 0.26). PC40V40p to bradykinin increased significantly in the placebo group (+2.46 +/- 0.92 DD, p = 0.04), with a similar trend for PC20FEV1 (+1.50 +/- 0.62 DD, p = 0.06), whereas there were no significant changes in the RV16 group (p > or = 0.77). These changes in PC40V40p to histamine and bradykinin were significantly different between the groups (p = 0.02). We conclude that repeated bradykinin challenge over a 10-d interval induces tachyphylaxis in asthmatic subjects in vivo and that experimental RV16 infection abolishes such tachyphylaxis to bradykinin while it enhances airway responsiveness to histamine. These results do not favor a predominant role of airway sensory nerves in rhinovirus-induced exacerbations of asthma.

Adult↗
PubMed1986

Characterization of the airway response to inhaled leukotriene D4 in normal subjects.

To better understand the role of leukotriene D4 (LTD4) in the pathogenesis of airway hyperreactivity, we administered aerosolized LTD4 on multiple occasions to 6 normal subjects and measured specific airway conductance (SGaw) by body plethysmography and the flow rate at 30% of vital capacity from partial forced expiratory maneuvers (V30P). Dose-response curves generated from standard bronchoprovocation tests revealed that LTD4 was 280 to 590 times more potent as a bronchoconstrictor than was methacholine. The airway response to single bronchoconstricting doses of LTD4 administered on separate days was reproducible for SGaw (r = 0.86, p less than 0.05) and V30P (r = 0.95, p less than 0.005). The response to 3 consecutive single-dose LTD4 challenges performed on the same day, allowing SGaw and V30P to return to greater than 90% of the control value between challenges, demonstrated tachyphylaxis: the response to the third dose was significantly less than the response to the first dose for SGaw (p less than 0.001) and for V30P (p less than 0.01). A single bronchoconstricting dose of LTD4, given before a standard methacholine dose-response challenge, lowered the concentration of methacholine needed to decrease V30P 30% (p less than 0.05) and SGaw 35% (p = 0.09). A single bronchoconstricting dose of methacholine preceding a standard methacholine challenge did not have this effect. LTD4 and methacholine demonstrated a cumulative dose-effect when progressively higher concentrations were inhaled. In summary, the airway response to LTD4 is reproducible, exhibits tachyphylaxis, and a cumulative dose-effect occurs. As well, LTD4 increases the responsiveness of normal airways to methacholine.

Adult↗
PubMed1987

Epidermal growth factor-urogastrone causes vasodilatation in the anesthetized dog.

Epidermal growth factor-urogastrone (EGF-URO) administered intraarterially was a potent dilator in dog femoral (FEM), superior (cephalic) mesenteric (SMA), celiac (CAC), coronary (COR), carotid (CAR), and renal (REN) vascular beds. The effects of EGF-URO, which exhibited tachyphylaxis, could not be attributed either to recirculating EGF-URO or to the secondary release of other agonists or products of the cyclooxygenase pathway. Two vascular beds (FEM, SMA) showed a high maximum responsiveness to EGF-URO (maximum effect [Emax] approximately equal to 70% increase in flow) whereas another group (CAC, COR, CAR, and REN) exhibited lower responsiveness (Emax approximately equal to 20%). The ED50 for this effect of EGF-URO was in the range of 0.4 micrograms (FEM, SMA, CAR, and COR) to 0.9 micrograms (CAC and REN). In isolated dog COR helical strips, EGF-URO did not exhibit either a direct relaxing or a contractile effect. However, preincubation of strips with EGF-URO caused up to a 66% inhibition of contraction in response to norepinephrine (1 microM), with an ED50 for EGF-URO of 1 nM. This action of EGF-URO also showed marked tachyphylaxis. Our data point to a potential role for EGF-URO (and possibly for the structurally related alpha-transforming growth factor) in the regulation of blood flow in vivo.

Animals↗
PubMed1991

Modulation of angiotensin II-induced vasoconstriction by endothelium-derived relaxing factor in the isolated microperfused rabbit afferent arteriole.

Although endothelium-derived relaxing factor (EDRF) has been studied extensively in large vessels, little is known about its role in the preglomerular afferent arteriole (Af-Art). We tested the hypothesis that EDRF, which is produced locally in the Af-Art, modulates arteriolar responses to angiotensin II (AII). A single rabbit Af-Art with its glomerulus intact was microperfused in vitro at 60 mmHg. When 0.1 microM AII was first applied, luminal diameter decreased by 49 +/- 7.0% (n = 9; P less than 0.0001); however, constriction waned, with the decrease becoming 15 +/- 3.5% at 1 min. After washing the Af-Art, repeated AII caused less constriction (13 +/- 4.0%; P less than 0.0002 vs. first application), showing tachyphylaxis. Pretreatment with Nw-nitro-L-arginine (N-Arg), which inhibits synthesis of nitric oxide (an EDRF), decreased basal diameter by 18 +/- 3.0% (n = 14; P less than 0.0001). N-Arg also augmented AII-induced constriction (86 +/- 6.8%; P less than 0.02 vs. nontreated Af-Art) and rendered it persistent (82 +/- 6.9% at 1 min). Even after pretreatment with N-Arg, repeated AII caused a weaker response, which was restored by washing with kidney homogenate rich in angiotensinase. In conclusion, this study provides evidence that local production of EDRF is an important determinant of the tone of the Af-Art. Our results suggest that the transient nature of AII-induced constriction of the Af-Art may be due to production of EDRF, while tachyphylaxis may be the result of long lasting receptor occupancy.

Angiotensin II↗
PubMed1996

Acute bronchial obstruction following inhalation of PAF in asthmatic and normal subjects: comparison with methacholine.

Platelet-activating factor (PAF) may play a role in the pathophysiology of asthma but controversies exist about bronchial responsiveness toward this mediator in asthma. We have compared the variations in the specific conductance (sGaw) and forced expiratory volume in one second (FEV1) in 12 asthmatics and 12 normal subjects after inhalation of doubling doses of PAF (15-120 micrograms) and methacholine (18 to at least 144 micrograms). In order to take into account a possible tachyphylaxis, we compared PAF dose-response curves performed on one day with the curves obtained by giving the same doses separately on different days. Repeated inhalations of doubling doses of PAF caused sGaw and FEV1 to plateau after the second dose in each group, whereas methacholine provoked a dose-related decrease in sGaw and FEV1. A dose-dependent decrease in the functional indices was restored when the different doses of PAF were administered on separate days. In both groups, the fall in sGaw after inhalation of 60 micrograms as a single dose was higher than that achieved when this dose was given during a full bronchial challenge. The falls in sGaw and FEV1 after PAF inhalation were significantly higher in the asthmatics than in the normal subjects. The provocative dose of PAF causing a 35% fall in sGaw (PD35,sGaw) PAF was only twofold lower in the asthmatics than in the normal subjects (p < 0.05), while it was 11 fold lower for methacholine (p < 0.001). When the PD35,sGaw values were compared, PAF was found on a molar basis to be 33 fold more potent than methacholine in the normal subjects, but only fivefold more potent in the asthmatics (p < 0.05). The percentage falls in FEV1 (calculated by interpolation) for a 35% fall in sGaw, were greater in asthmatics than in normals both for methacholine (p < 0.05) and PAF (p = 0.09). Our results demonstrate a tachyphylaxis after inhalation of platelet-activating factor in normal subjects and asthmatics, and show that asthmatics develop a greater bronchial obstruction than normal subjects even if methacholine is more sensitive than platelet-activating factor at discriminating between the two groups.

Administration, Inhalation↗
PubMed1984

Effect of sodium propionate on the contractile response of the rat ileum in situ.

Effects of short-chain fatty acids (SCFA) on the contractile response of rat ileum were studied in vivo. The contractile response was estimated by means of changes in the intraluminal pressure under the isometric condition. Intravenous administration of sodium salts of propionate, butyrate, valerate or caproate produced biphasic contractions: an initial phasic contraction and a subsequent tonic contraction. The effect of propionate was studied in detail. A sigmoid dose-response curve was obtained for the phasic contraction. Atropine, hexamethonium and tetrodotoxin inhibited the phasic contraction, while neostigmine vigorously enhanced it. On the other hand, the tonic contraction was not inhibited by atropine, hexamethonium or tetrodotoxin. Repeated administration of propionate at intervals of less than 3 min led to tachyphylaxis, and this tachyphylaxis disappeared by about 10 min. These results suggest that SCFA induced the biphasic contraction of the rat ileum, probably by neurogenic and myogenic mechanisms.

Animals↗
PubMed1975

Effect of nicotine on the lower esophageal sphincter. Studies on the mechanism of action.

Intravenous administration of nicotine sulfate caused a dose-dependent reduction in the lower exophagel sphincter pressure in anesthetized opossums. The maximal reduction in pressure of 85.0 +/- 2.6% was observed with a dose of 50 mug per kg. The effect of 50 mug per kg was not antagonized by bilateral cervical vagotomy, atropine, propranolol or by catecholamine depletion with reserpine. The sphincter relaxation produced by 50 mug per kg of nicotine was antagonized during tachyphylaxis produced by a larger dose (4 mg per kg) of nicotine. Nicotine tachyphylaxis also blocked the vagal-stimulated relaxation of the sphincter. It is suggested that the main action of nicotine on the sphincter in intact animals is caused by its effect on the noncholinergic, nonadrenergic inhibitory neurons which lie in the vagal pathway to the lower esophageal sphincter.

Animals↗