CHARACTERIZATION OF HISTAMINE H-3 RECEPTORS IN GUINEA-PIG ILEUM WITH H-3 SELECTIVE LIGANDS

1. The effect of the selective histamine H3-receptor agonist R-(α)-methylhistamine has been investigated on the contractile reponses of the longitudinal smooth muscle of guinea-pig ileum elicited by electrical field stimulation of acetylcholine release from myenteric nerve endings. 2. R-(α)-methylhistamine produced a concentration-dependent (EC50 = 1.4 ± 0.2 x 10-8 M) inhibition of the response to electrical field stimulation which was insensitive to inhibition by mepyramine (1 μM) and tiotidine (2.4 μM). 3. This reponse to R-(α)-methylhistamine could be inhibited in a competitive fashion by a range of H3-receptor antagonists including thioperamide (K(B) = 1.1 nM), impromidine (K(B) = 65 nM), norburimamide (K(B) = 380 nM) and SKF 91486 (K(B) = 34 nM). Burimamide was also a potent inhibitor of this response but the Schild slope obtained (1.3) was significantly greater than unity. 4. The estimated K(B) values were all within a factor of three of those values reported for the histamine release in rat cerebral cortex. 5. These data suggest that the histamine receptor mediating inhibition of cholinergic neurotransmission by R-(α)-methylhistamine in guinea-pig ileum is the same as the H3-receptor present in rat cerebral cortex.