CELL PHYSIOLOGY AND MOLECULAR PHARMACOLOG Y OF BRONCHIAL SMOOTH-MUSCLE

Bronchial smooth muscle is one of the main effectors of bronchial reac tivity. Considerable progress has been made over recent years in the u nderstanding of the cellular mechanisms of smooth muscle contraction b y the use of isolated cell study techniques. Extracellular messengers (neurotransmitters, mediators) and their specific membrane receptors h ave been analysed in detail. The membrane transduction of the extracel lular messenger allows the formation (or an increased concentration) o f the intracellular second messenger. In bronchial smooth muscle, this second messenger is the calcium ion. The extracellular messenger incr eases the cytoplasmic free calcium concentration (Ca-i(++)), via mecha nisms involving calcium channels and therefore dependent on the membra ne potential (electromechanical coupling), and especially mechanisms i ndependent of the membrane potential involving the metabolism of membr ane phosphoinositides (pharmacomechanical coupling). Variations of Ca- i(++) induce sliding of contractile filaments, responsible for shorten ing and tension, via controlled mechanisms such as phosphorylation of myosin or altered sensitivity of the contractile apparatus to Ca-i(++) . Experimental techniques allowing the simultaneous study of several a spects of the cellular response should provide, in the near future, fu rther information concerning cell physiology and molecular pharmacolog y of bronchial smooth muscle.