H3-receptor regulation of vascular gastrin and somatostatin releases by the isolated rat stomach.
We have studied the effects of the H3-receptor agonist (R) alpha-methylhistamine [(R) alpha-MeHA] and the H3-receptor antagonist thioperamide (Thiop) on basal- and carbachol-stimulated vascular gastrin release (GR) and somatostatin release (SR) by the isolated rat stomach. Carbachol dose-dependently stimulated and inhibited GR and SR, respectively. Maximal stimulation of GR (500 +/- 112 percent of basal; p < .01), and maximal inhibition of SR (-62 +/- 9 percent under basal; p < .01) were obtained with 1 micron carbachol. Neither (R)alpha-MeHA nor Thiop, up to 10 microns, affected GR. However, SR was dose-dependently enhanced by Thiop (25 +/- 8 percent for 10 microns). Carbachol stimulation of GR was strongly inhibited by Thiop (30 +/- 7 percent for 100 nM and 73 +/- 14 percent for 1 microgram), whereas it was potentiated by (R)alpha-MeHA. Carbachol inhibition of SR was reversed by Thiop and (R)alpha-MeHA. However, the reversal effect of (R)alpha-MeHA was prevented by the CCKB/gastrin receptor antagonist PD134308. These results support H3-receptor regulation of basal and cholinergically-stimulated GR and SR.
Bado
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Unité de Recherches de Gastroentérologie, INSERM Unité 10, Hôpital Bichat, Paris, France.
Moizo
L
L
Laigneau
J P
JP
Delwaide
J
J
Lewin
M J
MJ
D000818:Animals; D001808:Blood Vessels / Q000378:metabolism*; D002217:Carbachol / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005753:Gastric Mucosa / Q000378:metabolism*; D005755:Gastrins / Q000378:metabolism*; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008761:Methylhistamines / Q000494:pharmacology; D010477:Perfusion; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018100:Receptors, Histamine H3 / Q000378:metabolism*; D013004:Somatostatin / Q000378:metabolism*; D013270:Stomach / Q000098:blood supply
D005755:Gastrins; D017442:Histamine Agonists; D006633:Histamine Antagonists; D008761:Methylhistamines; D010880:Piperidines; D018100:Receptors, Histamine H3; D013004:Somatostatin; C069357:alpha-methylhistamine; D002217:Carbachol; C052075:thioperamide