5-HYDROXYTRYPTAMINE-INDUCED NO-DEPENDENT RELAXATION IN ISOLATED STRIPS OF MONKEY POPLITEAL LYMPH-NODES

5-Hydroxytryptamine (5-HT, 0.01-100 mu M) and 5-carboxamidotryptamine (5-CT, 0.001-10 mu M) produced dose-related relaxations in strips cut from monkey popliteal lymph nodes precontracted with a perfusion of Kr ebs bicarbonate solution containing 80 mM KC1. These 5-HT agonists cau sed no significant effect on the basal tone of the lymph node strips. The 5-HT-induced relaxation is competitively antagonized by pretreatme nt with a selective 5-HT1-like receptor antagonist, methiothepin (0.01 -0.1 mu M). Schild plot analysis showed that the pA(2) value and slope of methiothepin against 5-HT were 8.80 +/- 0.11 and 0.99 +/- 0.07 (n = 6), respectively. Pretreatment with methysergide (0.01-0.1 mu M) sig nificantly attenuated the 5-HT-induced relaxation of the strips. On th e other hand, treatment with ketanserin (0.01-0.1 mu M) and ICS-205-93 0 (0.01-0.1 mu M) caused no significant effect on the 5-HT-or the 5-CT -induced relaxation. The 5-HT-induced relaxation was significantly red uced by 10 mu M N-G-monomethyl-L-arginine, which was reversed by 1 mM L-arginine. The relaxation in the lymph node strips was also significa ntly reduced by treatment with 10 mu M methylene blue but not with 30 mu M aspirin. These results suggest that 5-HT1-like receptors exist in the monkey popliteal lymph nodes. Stimulation of these receptors prod uces an endogenous nitric oxide (NO)-dependent relaxation in lymph nod e smooth muscle through an activation of cytosolic guanylate cyclase i n the cells.