British journal of pharmacology
-
1. Small strips from third-order branches of rabbit mesenteric artery (approximately 150-200 microM wide) contracted in response to noradrenaline (10 microM) or 5-hydroxytryptamine (5-HT; 10 microM) in oxygenated Krebs solution containing 2.5 mM Ca2+. In a Ca(2+)-free mock intracellular solution (0 Ca2+ plus 0.2 mM EGTA), noradrenaline (10 microM) and caffeine (10 mM) induced only a single, transient contraction in artery strips, while 5-HT (10 microM) failed to induce any response. 2. ⋯ These results suggest that intracellular Ca2+ release does not play an important role in 5-HT-induced smooth muscle contraction in the rabbit mesenteric artery. This is despite the fact that a significant intracellular Ca2+ pool is present in these cells, which can be discharged by either noradrenaline or IP3. However, 5-HT did stimulate smooth muscle contraction in the presence of raised intracellular calcium,suggesting that a component of the contraction to 5-HT will reflect an increase in myofilament Ca2+sensitivity, possibly due to the activation of protein kinase C.
-
1. The histamine receptors were characterized on isolated circular segments of trachea and pulmonary arteries from the guinea-pig. The motor responses to histamine H1-, H2- and H3-receptor agonists and antagonists were tested and the responses obtained were analysed in relation to the respiratory epithelium and the vascular endothelium. 2. ⋯ In the guinea-pig trachea, histamine-induced contraction is mediated through H1-receptors where as dilatation probably involves an H3-receptor on the smooth muscle. The guinea-pig pulmonary artery appears to be endowed with a contractile H1 receptor on the smooth muscle cells and a dilator H1 receptor located on the endothelium. A dilator H2 receptor on the smooth muscle cells seems, at least in vitro, to be the most potent mediator of histamine-mediated pulmonary arterial dilatation.
-
1. GABAB agonists inhibit neuronal processes which are important in the pathogenesis of airway disease, such as bronchospasm. Cough is a prominent symptom of pulmonary disease, but the effects of GABAB agonists on this airway reflex are unknown. ⋯ In this model, baclofen (ED50 = 0.63 mg kg-1) was less potent than either codeine or dextromethorphan. The antitussive effect of baclofen in the cat was antagonized by the GABAB antagonists, CGP 35348 (10 mg kg-1, i.v.) and 3-aminopropylphosphonic acid (3 mg kg-1, i.v.).6. We show that baclofen and 3-APPi have antitussive effects in the guinea-pig and cat and these effects are mediated by GABAB receptors.
-
1. The formation of adenosine 3':5'-cyclic monophosphate (cyclic AMP) and inositol(1,4,5)trisphosphate (Ins(1,4,5)P3), induced by ATP and other nucleotides was investigated in mouse C2C12 myotubes. 2. ATP (100 microM) and ATP gamma S (100 microM) caused a sustained increase in cyclic AMP content of the cells, reaching a maximum after 10 min. ⋯ In contrast, UTP (30 microM-I mM) enhanced adenosine-induced cyclic AMP formation.8. Adenosine-sensitive P1-purinoceptors activating cyclic AMP formation were found in C2C12 myotubes. Further, a novel P2-purinoceptor is postulated, sensitive to ATP, ADP and ATPgammaS, which also activates the formation of cyclic AMP in C2C12 myotubes.
-
1. In vascular smooth muscle, alpha 1-adrenoceptors have been classified recently into two or three subtypes. We examined which alpha 1-adrenoceptor subtypes are involved in the noradrenaline-induced contraction of rat portal vein smooth muscle. 2. ⋯ The present results indicate the existence of two distinct o1-adrenoceptor subtypes in rat portal vein smooth muscle, which show high- and low-affinities respectively for each of prazosin, WB4101 andHV723 and correspond to alphalH- and alphalL-adrenoceptor subtypes. According to recent alpha1-adrenoceptor subclassifications, the alpha l H-adrenoceptor subtype which is sensitive to inactivation by CEC may correspond to the alpha1B-adrenoceptor subtype. The contraction induced by noradrenaline seems to be predominantly mediated through the alphalL-adrenoceptor subtypes which may include the alpha1N-adrenoceptor subtype, as recently proposed.