Search results for " Vitro"

Na+ ions binding to the bradykinin B2 receptor suppress agonist-independent receptor activation.

1996

Control of the balance between receptor activation and inactivation is a prerequisite for seven transmembrane domain (7TM) receptor function. We asked for a mechanism to stabilize the inactive receptor conformation which prevents agonist-independent receptor activation. Na+ ions have reciprocal effects on agonist versus antagonist interaction with various 7TM receptors. To investigate the Na+ dependence of receptor activation we chose the bradykinin B2 receptor as a prototypic 7TM receptor. Decrease of the intracellular Na+ content from 40 mM to 10 mM of COS-1 cells transiently expressing rat B2 receptors activated the B2 receptor in the absence of agonist as shown by a 3-fold increase in t…

The In Vitro Pharmacological Profile Of LAS100977 - A Potent, Selective And Long-acting Beta-2 Receptor Agonist

2010

Histaprodifens: synthesis, pharmacological in vitro evaluation, and molecular modeling of a new class of highly active and selective histamine H(1)-r…

2000

A new class of histamine analogues characterized by a 3, 3-diphenylpropyl substituent at the 2-position of the imidazole nucleus has been prepared outgoing from 4,4-diphenylbutyronitrile (4b) via cyclization of the corresponding methyl imidate 5b with 2-oxo-4-phthalimido-1-butyl acetate or 2-oxo-1,4-butandiol in liquid ammonia, followed by standard reactions. The title compounds displayed partial agonism on contractile H(1) receptors of the guinea-pig ileum and endothelium-denuded aorta, respectively, except 10 (histaprodifen; 2-[2-(3, 3-diphenylpropyl)-1H-imidazol-4-yl]ethanamine) which was a full agonist in the ileum assay. While 10 was equipotent with histamine (1), methylhistaprodifen (…

Purinoceptor-mediated modulation by endogenous and exogenous agonists of stimulation-evoked [3H]noradrenaline release on rat iris.

1992

To investigate whether endogenous purinoceptor agonists affect the sympathetic neurotransmission in the rat isolated iris, and to classify the purinoceptors modulating exocytotic [3H]-noradrenaline release, we have determined the effect of adenosine receptor antagonists on, and the relative potency of selected agonists in modulating, the field stimulation-evoked (3 Hz, 2 min) [3H]-noradrenaline overflow. In addition, the apparent affinity constants of 8-phenyltheophylline (8-PT) and 1,3-dipropyl-8-cyclopentylxanthine (DPCPX) in antagonizing the prejunctional effects of purinoceptor agonists were estimated. The relatively A1-selective DPCPX 10 and 100 nmol/l increased the evoked [3H]-noradre…

Effect of divalent cations on KCl- and noradrenaline-induced contractile responses in rat aorta after nifedipine treatment.

1999

Abstract Nifedipine (1 μM) relaxed the sustained contractile responses induced by 1 μM noradrenaline or 60 mM KCl in rat aortic strips. After washing, a second addition of the spasmogens gave smaller tonic contractions than the first one. Even more, a third addition of KCl also gave a smaller contraction than the first one, but a complete recovery of the contractile response to noradrenaline was obtained by a third addition of this agonist. Application of cumulative amounts of Ca2+ or Ba2+ (2.4–24 mM) on the residual contraction in response to these agents after nifedipine treatment, but in the absence of the blocker, restored the magnitude of the contractile responses. Addition of cumulati…

Interaction between cannabinoid CB1 receptors and endogenous ATP in the control of spontaneous mechanical activity in mouse ileum

2009

Background and purpose Although it is well accepted that cannabinoids modulate intestinal motility by reducing cholinergic neurotransmission mediated by CB(1) receptors, it is not known whether the endocannabinoids are involved in more complex circuits and if they interact with other systems. The aim of the present study was to examine possible interactions between cannabinoid CB(1) receptors and purines in the control of spontaneous contractility of longitudinal muscle in mouse ileum. Experimental approach The mechanical activity of longitudinally oriented ileal segments from mice was recorded as isometric contractions. Key results The selective CB(1) receptor agonist, N-(2-chloroethyl)5,8…

The 5-HT and alpha-adrenoceptor antagonist effect of four benzylisoquinoline alkaloids on rat aorta.

1998

Abstract The action of four benzylisoquinoline alkaloids (two aporphines—glaucine and apomorphine, a benzylisoquinoline—papaverine and a bisbenzyltetrahydroisoquinoline—antioquine) on 5-HT-induced contraction in rat thoracic aorta has been examined and compared with that of the control drugs: ketanserin, nifedipine, prazosin and phentolamine. The relaxant action on 5-HT-induced contraction was contrasted with that on the contraction induced by noradrenaline and KCl. The results obtained with control drugs show that ketanserin has clear selectivity for 5-HT receptors, whereas prazosin and phentolamine have high selectivity for the α1-adrenoceptor and nifedipine seems to have a more potent ef…

DIFFERENT ABILITY OF TRIFLUOPERAZINE TO INHIBIT AGONIST-INDUCED CONTRACTION OF LUNG PARENCHYMA STRIPS FROM CONTROL AND SENSITIZED GUINEA-PIGS

1988

Abstract There is increasing interest in the therapeutic potential of calcium antagonists in asthma. Among them the use of calmodulin antagonists deserves consideration. In the present work the effect of trifluoperazine on contractions generated by different mechanisms (CaCl2, KCl, acetylcholine, histamine and 5-hydroxytryptamine) in lung parenchyma strip isolated from control and actively sensitized guinea-pigs has been studied. Trifluoperazine produced both in unsensitized and sensitized lung strips, a concentration-dependent, right, downward displacement of the concentration-response curves to the agonists used, although the sensitization procedure resulted in a potentiation in the abili…

Glycopyrronium bromide blocks differentially responses mediated by muscarinic receptor subtypes.

1993

To analyse the potency of glycopyrronium bromide in blocking responses mediated via subtypes of muscarinic receptors in vitro, we tried to determine its equilibrium dissociation constants at prejunctional muscarinic receptors inhibiting the twitch response of rabbit vas deferens (presumed M1 type), at M2 (paced at left atria), M3 (guinea pig ileum) muscarinic receptor subtypes and at the muscarinic receptor of the rabbit iris sphincter (not M1-M4, not m5). Glycopyrronium bromide shifted to the right the curve for inhibition of the twitch response induced by the agonist McN-A-343, and the methacholine-induced curves for inhibition of rat atrial contraction, and for tonic contraction of guine…

Tachykinin NK(2) receptors facilitate acetylcholine release from guinea-pig isolated trachea.

2000

The release of newly synthesised [3H]acetylcholine was evoked by electrical field stimulation (5 Hz, 600 pulses) of epithelium-deprived guinea-pig trachea strips after sensory neuropeptides depletion with 3 microM capsaicin. The selective tachykinin NK(2) receptor agonist [betaAla(8)]neurokinin A-(4-10) increased in a concentration-dependent manner the electrically-induced release of [3H]acetylcholine. The facilitatory effect was antagonised by the selective non-peptide tachykinin NK(2) receptor antagonist, SR 48968 (apparent pK(B) 8.9). The tachykinin NK(1) and NK(3) receptor agonists substance P methyl ester and senktide (both 10 and 100 nM), respectively, did not affect the evoked releas…