Involvement of β adrenergic receptors in spasmolytic effect of caulerpine on guinea pig ileum

Previously, we demonstrated that caulerpine has spasmolytic effect on guinea pig ileum. The aim of this study was to investigate pathways of its spasmolytic action. We test caulerpine against phasic contractions induced by carbachol in the circular layer of guinea pig ileum and this alkaloid did not inhibit these contractions, indicating that caulerpine did not interfering with the mobilisation of Ca²⁺ from intracellular stores. Additionally, the spasmolytic effect of caulerpine did not involve K⁺ channels. Furthermore, we observed that α₂-adrenergic receptors were not involved in the spasmolytic effect of caulerpine, since the relaxation curve induced by caulerpine was not shifted in the presence of yohimbine (α₂-adrenergic antagonist). However, in the presence of propranolol (β-adrenergic antagonist), the relaxation curve induced by caulerpine was right-shifted, resulting in a fivefold increase in EC₅₀. Thus, a possible mechanism for the spasmolytic action of caulerpine is the activation of β-adrenergic receptors.     

The distribution of beta-adrenergic receptors in guinea pig lungs and their changes in experimental allergic asthma

In this paper, the distribution of pulmonary beta-adrenergic receptors (beta-receptors) in normal and experimental allergic asthmatic guinea pigs was determined using autoradiographic method. The results showed that the distribution of beta-receptors in the lung sections was widespread. There was a significant decrease of beta-receptor density in several tissue structures of asthmatic guinea pig lungs compared with the controls, a 23.73% decrease in beta-receptor binding sites in bronchiolar smooth muscles and a 18.65% decrease in bronchial smooth muscles; a 23.53%, a 14.23% and a 17.16% decrease in bronchiolar epithelium, in bronchial epithelium and in alveolar epithelium respectively. The results indicated that the beta-receptor decrease in smooth muscles in experimental asthmatic guinea pig lungs might be one of the important factors which made the tension of smooth muscles increase. The relationship between the beta-receptor decrease of other sites and bronchial asthma needs to be studied further.     

11C-methiodide quinuclidinyl benzilate a muscarinic antagonist for in vivo studies of myocardial muscarinic receptors

A method for labeling MQNB (Methiodide quinuclidinyl benzilate) with carbon-11 using¹¹C-methyl iodide is reported. Injectable labeled product (100 mCi; max. 200 mCi) radiochemically and chemically pure is obtained in a 30 minute synthesis time with a specific activity of 1 Ci/μmol, (max. 2.3 Ci/μmol).     

Endothelin receptors in gastrointestinal smooth muscle

Endothelins (ETs) are a family of peptides with 21-amino-acid residues. ET-1 was identified as a potent vasoconstrictor produced by vascular endothelial cells. Three distinct isoforms of ET, i.e. ET-1, ET-2 and ET-3, have been found to exist in a variety of tissues. ET was later found to cause contraction as well as relaxation of smooth muscle in many physiologic systems. In the gastrointestinal tract, ET causes contraction and/or relaxation of the esophagus, stomach, ileum and colon. In the hepatobiliary system, ET causes contraction of the portal vein, hepatic stellate cells, gallbladder and common bile duct. In mammalian species, two classes of ET receptors, ET(A) and ET(B), have been cloned. ET(A) receptors have higher affinities for ET-1 and ET-2 than ET-3, while ET(B) receptors have the same affinities for ET-1, ET-2 and ET-3. In the gastrointestinal system, ET causes smooth muscle contraction through interaction with ET(A) receptors, ET(B) receptors or both ET(A) and ET(B) receptors, depending on the tissues and species. In addition to contraction, ET causes smooth muscle relaxation through interaction with ET(A) receptors or ET(B) receptors. At the present time, there are no studies showing that ET causes smooth muscle relaxation through interaction with both ET(A) and ET(B) subtypes. ET induces contraction in most of the non-sphincter muscle except the fundus of the stomach. On the other hand, ET causes relaxation and contraction in the lower esophageal and internal anal sphincters. ET may play an important role in the control of human gastrointestinal motility and portal vein pressure.     

Binding of agonists and antagonists to muscarinic receptors.

The binding of one irreversible and two reversible radioactive antagonists to muscarinic receptors in synaptosome preparations of rat cerebral cortex has been studied. The ligands all bind to the same receptor pool and directly and competitively yield self-consistent binding constants closely similar to those obtained by pharmacological methods on intact smooth muscle. The binding process for antagonists seems to be a simple mass action-determined process with a Hill slope of 1.0. The quantitative correlations strongly support the view that the receptor studied by ligand binding corresponds to the receptor studied by pharmacological methods. Inhibition of antagonist binding by most agonists shows a reduced Hill slope which also applies to direct binding studies of [3H] acetylcholine. Mechansims that might account for the behavior of agonists are discussed but do not conclusively point to any single mechanism.     

Determination of prostaglandin profiles in lipopolysaccharide‐challenged guinea pig spleen

We previously reported that splenic extract from lipopolysaccharide (LPS)‐challenged guinea pigs inhibits the exaggerated febrile response of splenectomized guinea pigs, suggesting that the spleen generates an inhibitory factor. Earlier results indicate that the factor is a lipid. In an effort to identify this factor, lipid fractions, isolated from splenic extracts of control and LPS‐challenged guinea pigs, were analyzed with emphasis on identifying and quantifying prostanoids, which according to current knowledge are the likely bioactive factors. Prostaglandins have been extensively implicated in central and peripheral thermoregulation, and thus these lipids were targeted for characterization in the spleen. Analysis was done on the splenic extracts using solid‐phase extraction, analytical and preparative thin‐layer chromatography (TLC) and high‐performance liquid chromatography–mass spectrometry (HPLC‐MS/MS). Four prostaglandins (PGs, 6‐keto‐PGF_1α, PGF_2α, PGE₂ and PGD₂) were identified and quantified. Our data shows that these PG levels are doubled in LPS‐treated guinea pig spleen compared with the control group. The methods used in this investigation to characterize PG in the spleen offer significant advantages over immunoassays previously used to identify and quantify PG in the spleen and other biological tissues. These methods will be utilized in further research needed to definitively characterize the role of splenic‐derived PG in modulation of the febrile response induced by LPS. Copyright © 2012 John Wiley & Sons, Ltd.     

Permeability of ionized salicylate derivatives through guinea pig dorsal skin

pH-dependency of skin permeability to salicylic acid was examined in excised guinea pig dorsal skin. Permeation followed the pH-partition theory at acidic pH. However, above pH 5.0 the observed permeability coefficients were larger than the estimated values obtained from the ratio of the undissociated forms. These findings are quite different from those obtained using the same drug and a silicone rubber membrane, in which permeability coefficients were consistent with the pH-partition theory. The findings suggested that permeation of salicylate as anions occurred at a neutral skin pH. The permeability coefficient of the ionized form was estimated to be about 1.6% of the nonionized form. We also examined the skin permeability of salicylate and its five 5-substituents and two 3-substituents at pH 7.4. We investigated the relationship between their permeability coefficients and the physico-chemical properties of the substituents. Multi regression analysis on the permeability coefficients showed a parabolic relationship between the values of the hydrophobic parameter (pi) and the logarithms of the permeability coefficients. These findings suggested that the ionic permeation pathway of salicylate derivatives is controlled by hydrophobic as well as hydrophilic properties.     

Anti-cholinergic effect of Zataria multiflora Boiss on guinea pig tracheal chains

The effects of three concentrations of aqueous-ethanolic extract, 10?nM atropine and saline on muscarinic receptors were tested on two groups of non-incubated (group 1; n?=?7) and incubated tracheal chains with propranolol and chlorpheniramine (group 2; n?=?6). The EC?? of higher concentration of the extract (2?μg?mL?1) in group 2 was significantly greater than those of group 1 (p?相似文献