Characterization of histamine H3‐receptors in guinea‐pig ileum with H3‐selective ligands

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Abstract
1 The effect of the selective histamine H3-receptor agonist R-(α)-methylhistamine has been investigated on the contractile responses 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 × 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 response to R-(α)-methylhistamine could be inhibited in a competitive fashion by a range of H3-receptor antagonists including thioperamide (KB = 1.1 nm), impromidine (KB = 65 nm), nor-burimamide (KB = 380 nm) and SKF 91486 (KB = 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 KB values were all within a factor of three of those values reported for the histamine H3-receptor mediating inhibition of 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.