Patricia Campos-Bedolla

Effect of kauranes from Montanoa spp. on rat uterus

The effect of kaurenoic acid (from Montanoa frutescens), grandifloric and kauradienoic acid (from M. tomentosa) and 16α‐hydroxy‐ent‐kauran‐19‐oic acid and its methyl ester (from M. hibiscifolia) were assayed on the contractions of rat uterus induced by acetylcholine, oxytocin and serotonin. The four kauranes assayed inhibited the contractile activity induced by the three agonists through a mechanism independent of either β2‐adrenergic or H2‐histaminergic receptors present in uterine smooth muscle. Oestrogenized uteri treated with kauradienoic acid underwent histological changes including epithelial flattening and desquamation.© 1997 John Wiley & Sons, Ltd.

Role of 5‐HT2A, 5‐HT4 and 5‐HT7 receptors in the antigen‐induced airway hyperresponsiveness in guinea‐pigs

Background A possible role of 5‐hydroxytryptamine (5‐HT) in the origin of antigen‐induced airway hyperresponsiveness (AI‐AHR) has been scarcely investigated.

Airway smooth muscle relaxation induced by 5-HT2A receptors: Role of Na+/K+-ATPase pump and Ca2+-activated K+ channels

AIMS Although 5-hydroxytryptamine (5-HT) contracts airway smooth muscle in many mammalian species, in guinea pig and human airways 5-HT causes a contraction followed by relaxation. This study explored potential mechanisms involved in the relaxation induced by 5-HT. MAIN METHODS Using organ baths, patch clamp, and intracellular Ca(2+) measurement techniques, the effect of 5-HT on guinea pig airway smooth muscle was studied. KEY FINDINGS A wide range of 5-HT concentrations caused a biphasic response of tracheal rings. Response to 32 microM 5-HT was notably reduced by either tropisetron or methiothepin, and almost abolished by their combination. Incubation with 10 nM ketanserin significantly prevented the relaxing phase. Likewise, incubation with 100 nM charybdotoxin or 320 nM iberiotoxin and at less extent with 10 microM ouabain caused a significant reduction of the relaxing phase induced by 5-HT. Propranolol, L-NAME and 5-HT(1A), 5-HT(1B)/5-HT(1D) and 5-HT(2B) receptors antagonist did not modify this relaxation. Tracheas from sensitized animals displayed reduced relaxation as compared with controls. In tracheas precontracted with histamine, a concentration response curve to 5-HT (32, 100 and 320 microM) induced relaxation and this effect was abolished by charybdotoxin, iberiotoxin or ketanserin. In single myocytes, 5-HT in the presence of 3 mM 4-AP notably increased the K(+) currents (I(K(Ca))), and they were completely abolished by charybdotoxin, iberiotoxin or ketanserin. SIGNIFICANCE During the relaxation induced by 5-HT two major mechanisms seem to be involved: stimulation of the Na(+)/K(+)-ATPase pump, and increasing activity of the high-conductance Ca(2+)-activated K(+) channels, probably via 5-HT(2A) receptors.

Allergic sensitization modifies the pulmonary expression of 5-hydroxytryptamine receptors in guinea pigs

There is mounting evidence that 5-hydroxytryptamine (5-HT) plays a role in asthma. However, scarce information exists about the pulmonary expression of 5-HT receptors and its modification after allergic sensitization. In the present work, we explored the expression of 5-HT1A, 5-HT2A, 5-HT3, 5-HT4, 5-ht5a, 5-HT6, and 5-HT7 receptors in lungs from control and sensitized guinea pigs through qPCR and Western blot. In control animals, mRNA from all receptors was detectable in lung homogenates, especially from 5-HT2A and 5-HT4 receptors. Sensitized animals had decreased mRNA expression of 5-HT2A and 5-HT4 receptors and increased that of 5-HT7 receptor. In contrast, they had increased protein expression of 5-HT2A receptor in bronchial epithelium and of 5-HT4 receptor in lung parenchyma. The degree of airway response to the allergic challenge was inversely correlated with mRNA expression of the 5-HT1A receptor. In summary, our results showed that major 5-HT receptor subtypes are constitutively expressed in the guinea pig lung, and that allergic sensitization modifies the expression of 5-HT2A, 5-HT4, and 5-HT7 receptors.

Modifications of plasma 5-HT concentrations during the allergic bronchoconstriction in guinea pigs

ABSTRACT Several contractile mediators involved in the antigen-induced airway obstruction have been identified, but the role of 5-HT (5-hydroxytryptamine or serotonin) has been scantily investigated. In this work, the potential role of 5-HT in the allergic bronchoconstriction was evaluated through a pharmacological approach and plasma 5-HT measurement in blood samples from the right and left ventricles of anesthetized guinea-pigs. Intravenous 5-HT caused a dose-dependent increase of the lung resistance in anesthetized, nonsensitized guinea pigs. Likewise, in sensitized animals the antigenic challenge with ovalbumin also caused a transient bronchoconstriction (356 ± 60% the basal value), which was largely inhibited by the blockade of serotonergic receptors with methiothepin plus tropisetron (134 ± 10%, P = .007). Sensitized animals tended to have plasma 5-HT concentrations higher than nonsensitized controls, and shortly after the peak of the allergic bronchoconstriction the 5-HT levels in the left ventricle (blood flowing out from lungs) tended to be higher than in the right ventricle (blood entering the lungs), although data dispersion precluded the obtaining of statistical significance. Interestingly, the degree of bronchoconstriction highly correlated with the concentrations of 5-HT found in the left ventricle and measured either in platelet-rich plasma (r = 0.97 P = .007) or platelet-poor plasma (r = 0.97, P = .006). After the obstructive response subsided these correlations were lost, but now the degree of bronchoconstriction turned to be correlated with 5-HT concentration in platelet concentrate (r = 0.76, P = .03). In conclusion, our results suggested that 5-HT is actively released from lungs during the antigenic challenge and that this autacoid is involved in the generation of the airway obstruction.

Effect of acute ozone exposure on pregnant rat uterus contractile responses.

Pulmonary effects of ozone (O(3)) inhalation have been comprehensively studied, but little is known about its extrapulmonary consequences, particularly in the reproductive tract. Thus, the effects of an acute O(3) exposure on the contractile response of the pregnant rat uterus were evaluated. Nonpregnant and pregnant (5, 10, and 18 days of gestation) rats were exposed to air or O(3) (3 ppm) for1 h, and uterine strips isolated from these animals were studied 16-18 h later. Contractile responses to acetylcholine (ACh) and oxytocin (OT) were evaluated with respect to three parameters (area under the curve, amplitude, and frequency). O(3) did not modify the sensitivity (-logEC(50)) to either agonist at any pregnancy stage, but induced a statistically significant increase in all maximum responses to OT at gestational day 5, and increased the maximum response (area under the curve) to ACh at pregnancy days 5 and 10. Our results suggest that O(3) inhalation can produce abnormal contractility in the pregnant uterus, and identify the need for further investigation of this issue.

Asociación inversa entre asma y defectos del tubo neural: estudio ecológico binacional

Objective. Dietary intake of methyl donors such as folic acid prevents neural tube defects (NTD), but recent studies showed that it might also favor the development of asthma. In this work a possible ecological association between NTD and asthma was explored. Material and Methods. Data bases from Mexico and the United States (US) were reviewed to obtain information about geographical distribution (by state) and temporal trends (by year) of NTD and asthma. Results. Those states with the lowest frequency of NTD had the highest frequency of asthma, both in Mexico (r S =-0.48, p=0.005) and US (r S =-0.39, p=0.005). Temporal trends also showed an inverse correlation in Mexico (1997-2007, r S =-0.73, p=0.01) and US (1979-1998, r S =-0.91, p<0.001). Conclusions. In both countries the frequency of asthma inversely correlated with the frequency of NTD, both in geographical distribution and annual trends, giving support to the possibility that methyl donors intake in diet or supplements is influencing the asthma frequency.