The guinea pig tracheal contractile serotonergic receptor shows pharmacological similarity to both 5-hydroxytryptamine2 (5-HT2) and 5-hydroxytryptamine1C (5-HT1C) receptors. The present in vitro study utilizes 5-methyltryptamine (5-MT), a high-affinity 5-HT1C receptor ligand, and dipropyl-5-carboxamidotryptamine (DP-5-CT), a low-affinity 5-HT1C receptor ligand, as tools to probe the role of 5-HT1C vs. 5-HT2 receptors in tracheal contractility. Both tryptamines contracted trachea with lower potency (-log EC50 < 5) than 5-HT (-log EC50 = 6.98). Maximum contraction to both 5-MT and DP-5-CT was only 50 to 80% of the maximum response to 5-HT, suggesting that these compounds were partial agonists relative to 5-HT. Guinea pig tracheal contraction to 5-HT, 5-MT and DP-5-CT was inhibited by 1-(1-naphthyl)piperazine (1-NP, 30 nM). The apparent antagonist dissociation constants (KB) for 1-NP were similar when 5-HT (-log KB, K = 8.70 +/- 0.17) or 5-MT (- log KB = 8.40 +/- 0.12) were used as agonists. Although 1-NP also blocked tracheal contraction to DP-5-CT, solubility limitations with DP-5-CT did not permit calculation of a KB value for 1-NP. Nevertheless, these data indicate that 5-MT and DP-5-CT interact with the same receptor as 5-HT. As antagonists, both 5-MT and DP-5-CT inhibited tracheal contraction to 5-HT, indicating interaction with the same receptor as 5-HT and confirming partial serotonergic agonist activity.(ABSTRACT TRUNCATED AT 250 WORDS)