H1-RECEPTOR-MEDIATED EXCITATION AND FACILITATION OF THE HEAT RESPONSEBY HISTAMINE IN CANINE VISCERAL POLYMODAL RECEPTORS STUDIED IN-VITRO

1. We examined excitation and the facilitatory effect on the heat resp onses induced by histamine in visceral polymodal receptors with the us e of the canine testis-spermatic nerve preparation in vitro. 2. The pr oportion of units that showed excitation (>10 impulses 1 min after app lication of histamine was initiated) increased roughly with higher con centrations of histamine: 7% at 1 mu M, 26% at 10 mu M, 79% at 100 mu M, and 61% at 1,000 mu M. The discharge rate also increased with the c oncentration. 3. Histamine (100 and 1,000 mu M) responses >0.5 imp/s w ere observed only in units with conduction velocities (CVs) of less th an or equal to 10 m/s, but not in those with CVs faster than 10 m/s. O n average. histamine-induced discharges were significantly greater in units with CVs of less than or equal to 10 m/s at all concentrations g reater than or equal to 10 mu M. Thus units studied in this experiment were empirically divided into slow-CV (less than or equal to 10 m/s) and fast-CV (>10 m/s) groups. 4. Histamine significantly facilitated t he heat responses of the slow-CV group from 10 mu M; and also facilita ted the fast-CV group from 100 mu M. This sensitizing effect was obser ved irrespective of the precedent histamine-induced excitation. The ma gnitude of sensitization tended to increase with an increase in histam ine concentration. 5. For studying the histamine receptor subtype invo lved in excitation and facilitation, we used D-chlorpheniramine maleat e (5 mu M) (an H1 receptor antagonist), famotidine (20 mu M) (an H2 re ceptor antagonist), and thioperamide maleate (20 mu M) (an H3 receptor antagonist). The magnitude of histamine-induced excitation of the slo w-CV group was significantly suppressed by the H1 receptor antagonist but not by other antagonists. 6. The facilitatory effect of histamine on the heat response was also suppressed by the H1 receptor antagonist in both slow- and fast-CV groups. 7. These results strongly suggest t hat both excitation and facilitation of the heat response induced by h istamine are mediated through the H1 receptor.