Histamine H3-receptor-induced inhibition of duodenal cholinergic transmission is independent of intracellular cyclic AMP and GMP.
1. The inhibitory effect of the histamine H3-receptor agonist (R) alpha-methylhistamine on cholinergic neurotransmission was studied in the isolated guinea pig duodenum in the presence of different compounds which alter intracellular levels of cyclic nucleotides and of the G proteins blocker pertussis toxin. 2. The action of (R) alpha-methylhistamine on electrically-evoked contractions was not modified either by forskolin and isobutylmethylxanthine (which increase cyclic AMP) or by zaprinast and methylene blue (which increase and decrease, respectively intracellular cyclic GMP). Drugs affecting cyclic nucleotide levels were also ineffective against the inhibitory effect of the alpha 2 adrenergic agonist clonidine. 3. Pertussis toxin significantly reduced the maximum inhibition induced by (R) alpha-methylhistamine and clonidine, without influencing the effect of low concentrations of the above compounds; conversely it shifted to the right in a parallel way the inhibitory effect of adenosine. 4. These data suggest that H3-receptor-mediated inhibition of cholinergic transmission in the guinea pig duodenum is not linked to intracellular nucleotide changes. Moreover the signal transducing mechanism activated by (R) alpha-methylhistamine involves pertussis toxin both sensitive and insensitive G proteins.
Poli
E
E
Institute of Pharmacology, University of Parma, Italy.
Pozzoli
C
C
Coruzzi
G
G
Bertaccini
G
G
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000037:antagonists & inhibitors; D000241:Adenosine / Q000494:pharmacology; D000818:Animals; D003000:Clonidine / Q000494:pharmacology; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism / Q000502:physiology*; D006152:Cyclic GMP / Q000378:metabolism / Q000502:physiology*; D004386:Duodenum / Q000187:drug effects / Q000294:innervation; D006168:Guinea Pigs; D017442:Histamine Agonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D010275:Parasympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D018100:Receptors, Histamine H3 / Q000187:drug effects / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*
D017442:Histamine Agonists; D008761:Methylhistamines; D018100:Receptors, Histamine H3; D005576:Colforsin; C069357:alpha-methylhistamine; D000242:Cyclic AMP; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D006152:Cyclic GMP; D000241:Adenosine; D003000:Clonidine; D015056:1-Methyl-3-isobutylxanthine