5-HT2-mediated bronchial responses after syngeneic lung transplantation in the rat.

Abstract

1. The effect of lung transplantation was assessed on the subsequent bronchial responses to 5-hydroxytryptamine (5-HT) in the rat in vitro. 2. Bronchial ring segments from syngeneic lung transplant recipients, from sham-operated and from non-operated control animals were studied in organ baths one month after unilateral left lung transplantation. 3. Responses of the bronchial smooth muscle to 5-HT (10(-8) to 10(-4) M) significantly increased after lung transplantation (80.6 +/- 7.6% of the maximal contractile response to acetylcholine) compared with the responses of all other controls (ca. 40% of the maximal contractile response to acetylcholine, P < 0.01). pD2 values were similar for the left transplanted (5.70 +/- 0.11) and all other control bronchi (ranging from 5.53 to 5.82). 4. Contraction to 5-HT was blocked by the selective 5-HT2 antagonist, ketanserin. Responses to the selective 5-HT2 agonist, alpha-methyl-5-HT, were similar to those to 5-HT; pD2 values were similar in all groups (ranging from 5.41 to 5.74). 5. The selective 5-HT3 agonist, 1-m-chlorophenyl biguanide, had no contractile effect on rat bronchus, whether transplanted or not. 6. Atropine, a muscarinic cholinoceptor blocking agent, had no effect on 5-HT-induced bronchial contraction. Hence, acetylcholine released from nerve terminals does not play any role in the observed bronchial hyperresponsiveness to 5-HT. 7. These results show bronchial hyperresponsiveness to 5-HT in vitro one month after lung transplantation in the rat, mediated through 5-HT2 receptor activation. This might be caused by upregulation of 5-HT2 receptors in the lung after transplantation.