Characterization of histamine H3-receptors in guinea-pig ileum with H3-selective ligands.
1. The effect of the selective histamine H3-receptor agonist R-(alpha)-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-(alpha)-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 microM) and tiotidine (2.4 microM). 3. This response to R-(alpha)-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), norburimamide (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-(alpha)-methylhistamine in guinea-pig ileum is the same as the H3-receptor present in rat cerebral cortex.
Hew
R W
RW
Department of Physiology & Pharmacology, Medical School, Queen's Medical Centre, Nottingham.
Hodgkinson
C R
CR
Hill
S J
SJ
D000818:Animals; D004558:Electric Stimulation; D005260:Female; D006146:Guanidines / Q000494:pharmacology; D006168:Guinea Pigs; D007082:Ileum / Q000187:drug effects / Q000378:metabolism*; D007093:Imidazoles / Q000494:pharmacology; D017446:Impromidine; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects / Q000378:metabolism; D010425:Pentolinium Tartrate / Q000494:pharmacology; D010880:Piperidines / Q000494:pharmacology; D011968:Receptors, Histamine / Q000187:drug effects / Q000378:metabolism*; D018100:Receptors, Histamine H3
D006146:Guanidines; D007093:Imidazoles; D008761:Methylhistamines; D010880:Piperidines; D011968:Receptors, Histamine; D018100:Receptors, Histamine H3; D017446:Impromidine; D010425:Pentolinium Tartrate; C052075:thioperamide