Effects and interactions of opioids on plasma exudation induced by cigarette smoke in guinea pig bronchi

The effects of opioids on cigarette smoke-induced plasma exudation Were inv estigated in vivo in the main bronchi of anesthetized guinea pigs, with Eva ns blue dye as a plasma marker. Acute inhalation of cigarette smoke increas ed plasma exudation by 216% above air control values. Morphine, 0.1-10 mg/k g but not 30 mg/kg, inhibited the exudation but had no significant effect o n substance P-induced exudation. Both 10 and 30 mg/kg of morphine increased exudation in air control animals, an effect inhibited by antihistamines bu t not by a tachykinin neurokinin type 1-receptor antagonist. Naloxone inhib ited all morphine responses. Cigarette smoke-induced plasma exudation was i nhibited by a mu-opioid-receptor agonist (DAMGO) but not by agonists at del ta (DPDPE)- or kappa (U-50488H)-receptors. None of these agonists affected exudation in air control animals. DPDPE prevented the inhibition by DAMGO o f cigarette smoke-induced plasma exudation, and the combination of DAMGO an d DPDPE increased exudation in air Control animals. Prevention of inhibitio n and the combination-induced increase were inhibited by antihistamines or the mast cell-stabilizing drug sodium cromoglycate. U-50488H did not alter the response to either DAMGO or DPDPE. We conclude that, in guinea pig main bronchi in vivo, mu-opioid-receptor agonists inhibit cigarette smoke-induc ed plasma exudation via a prejunctional mechanism. Plasma exudation induced by mu- and delta-receptor interactions is due to endogenous histamine rele ase from mast cells.