Figure 4.

HTMT does not have agonist activity at the H₁ receptors expressed in mouse PO/AH neurons but antagonizes histamine effects. (A) [Ca]_i responses to histamine (100 μM) before during and after HTMT (30 μM) incubation. The trace represents the average of the responses from five cultured PO/AH neurons. Note that HTMT does not elicit an increase of [Ca]_i but decreases the histamine effect. (B) Concentration–response curve for the antagonist activity of HTMT on the [Ca]_i responses to histamine (100 μM). Each point represents the average of data collected from 20 different PO/AH neurons. The data were fitted with a logistic function. The fit yielded an IC₅₀ of 19 μM. (C) Inward current activated by histamine (100 μM) before and during HTMT (100 μM) incubation recorded in a cultured PO/AH neurons. HTMT does not activate inward current but decreases the histamine effect. The holding potential was −50 mV. (D) Concentration–response curve for the antagonist activity of HTMT on the inward current activated by histamine (100 μM). Each point represents the average of data collected from six different PO/AH neurons. The data were fitted with a logistic function. The fit yielded an IC₅₀ of 16 μM. (E) Short incubations (40 s) with histamine or H₁ receptor agonists do not induce long lasting desensitization. The traces are responses from individual cells and are representative of the average response of PO/AH neurons. (F) Mepyramine (0.1 μM) blocks the responses activated by methylhistaprodifen (MH; 100 μM) and 2-(3-TFMP) histamine (100 μM). The traces are representative responses of individual PO/AH neurons. (E, F) Response was recorded from PO/AH cultures from C57/Bl6 mice. (A–F) TTX (1 μM), CNQX (20 μM), AP-5 (50 μM) and bicuculline (20 μM) were present in the extracellular solution.