The histamine H-3 receptor shows high degree of stereoselectivity for histamine analogues branched in the side chain. The hypothesis that gastroprotection by (R)-alpha-methylhistamine could be H-3 receptor-mediated was tested by comparing the effect: of (R)-alpha-methylhistamine and of (S)-alpha-methylhistamine on ethanol-induced histologic lesions in the mt gastric mucosa. Extensive damage was caused by 60 min exposure to absolute ethanol, 91% of the mucosa examined being damaged. Conversely only 23% of the mucose was damaged after pretreatment with (R)-alpha-methylhistamine (100 mg/kg i.g.). In the groups pretreated with (S)-alpha-methylhistamine (55.44 and 166.3 mg/kg i.g.) total damage ranged from 77 to 79%, though it was confined to the upper portion of the mucose. Morphometric analysis of stained intraepithelial mucosubstances revealed that (R)-alpha-methylhistamine pretreatment resulted in an increase in number and volume of surface mucous cells, not evident after (S)-alpha-methylhistamine pretreatment. Scanning electron microscopy confirmed light microscopy evaluations. The two isomers of alpha-methylhistamine differently affect the response of rat gastric mucose to absolute ethanol and they appear to differ in their influence on surface mucous cells. A basis for interpreting the effects of the two isomers of a-methylhistamine rests on the high degree of stereoselectivity of H-3 receptors and on the different affinities of the two isomers for these receptors.

Stereoselective Inhibition of Ethenol-Induced Gastric Lesions in the Rat by the H3-Receptor Agonist (R)-alfa-Methylhistamine and Its (S)-Configured Isomer / MORINI G.; GRANDI D.; BERTACCINI G.; LESCHKE C.; SCHUNACK W.. - In: PHARMACOLOGY. - ISSN 0031-7012. - 59(1999), pp. 192-200. [10.1159/000028320]

Stereoselective Inhibition of Ethenol-Induced Gastric Lesions in the Rat by the H3-Receptor Agonist (R)-alfa-Methylhistamine and Its (S)-Configured Isomer

MORINI, Giuseppina;GRANDI, Daniela;
1999

Abstract

The histamine H-3 receptor shows high degree of stereoselectivity for histamine analogues branched in the side chain. The hypothesis that gastroprotection by (R)-alpha-methylhistamine could be H-3 receptor-mediated was tested by comparing the effect: of (R)-alpha-methylhistamine and of (S)-alpha-methylhistamine on ethanol-induced histologic lesions in the mt gastric mucosa. Extensive damage was caused by 60 min exposure to absolute ethanol, 91% of the mucosa examined being damaged. Conversely only 23% of the mucose was damaged after pretreatment with (R)-alpha-methylhistamine (100 mg/kg i.g.). In the groups pretreated with (S)-alpha-methylhistamine (55.44 and 166.3 mg/kg i.g.) total damage ranged from 77 to 79%, though it was confined to the upper portion of the mucose. Morphometric analysis of stained intraepithelial mucosubstances revealed that (R)-alpha-methylhistamine pretreatment resulted in an increase in number and volume of surface mucous cells, not evident after (S)-alpha-methylhistamine pretreatment. Scanning electron microscopy confirmed light microscopy evaluations. The two isomers of alpha-methylhistamine differently affect the response of rat gastric mucose to absolute ethanol and they appear to differ in their influence on surface mucous cells. A basis for interpreting the effects of the two isomers of a-methylhistamine rests on the high degree of stereoselectivity of H-3 receptors and on the different affinities of the two isomers for these receptors.
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11381/1454802
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 10
  • ???jsp.display-item.citation.isi??? 7
social impact