Actions of second messengers synthesised by various spasmogenic agents and their relation to mechanical responses in dog tracheal smooth muscle

The effects of spasmogenic agents, carbachol (CCh), histamine, 5-hydroxytryptamine (5-HT) and 9, 11-epithio-11,12-methano-thromboxane A_2 (STA_2 ) on smooth muscle tissues of dog trachea were investigated. Measurements were made of the mechanical responses, Ca^++ transients, cyclic nucleotides (cAMP and cGMP) and inositol 1,4,5-trisphosphate (IP_3 ). Among the above stimulant, CCh produced the largest contraction. In a Ca^++ -free (0.2mM EGTA) solution, only a phasic contraction was evoked by the above agents. CCh, histamine and 5-HT increased the amount of IP_3 , cellular Ca^++ and developed tension, concentration dependently. Synthesis of IP_3 induced by the above agents reached peak values within 30 sec and lasted for about 3 min. CCh slightly increased the amount of cAMP but not the other. 5-HT reduced, but histamine and CCh increased the amount of cGMP. CCh increased the Ca^++ transients from 180nM to 1.48 μM as measured using fura 2. The potency order among the stimulants were as follows： 1) on tension, CCh > histamine = 5-HT, 2) on Ca^++ -changes, CCh > 5-HT > histamine, 3) on IP_3 production, CCh > histamine > 5-HT. The potency order of the Ca^++ transient values correspond well to the amplitude of contraction but not with that of IP_3 . The different potency order of the stimulants between Ca^++ transients and IP_3 production may explain the different synthesis of cyclic nucleotides in the presence of stimulants.