Metabolism and Distribution of Exogenous Histamine in Cats

Abstract

1 The metabolism and disposition in blood and tissues of exogenous ["4C]-histamine was examined in cats.2 The principal metabolites in blood of histamine instilled into the small intestine (directly or by transfer from the stomach) and colon were imidazoleacetic acid and t-methylimidazoleacetic acid, being present in approximately equal amounts although in individual cats one or other acid could predominate. Only small amounts of histamine entered the circulation although in two of four cats given the largest dose (82 1imol/kg) large amounts were recovered. The amount of "4C radioactivity absorbed varied directly with the dose instilled. The chief metabolite in kidney and urine, whether histamine was instilled into the intestine or infused parenterally, was t-methylimidazoleacetic acid. Histamine was not absorbed from the stomach and its metabolism there was negligible. 3 In contrast, when histamine was infused into blood leaving the intestine (portal vein) the main metabolite in blood and tissues was t-methylimidazoleacetic acid being found in approximately 5-fold the concentration of imidazoleacetic acid. The small amount of histamine which eluded inactivation/uptake by liver, lungs, heart during the infusion was halved on circulation through the intestine. When histamine was infused into blood supplying the intestine, (cranial mesenteric artery) t-methylimidazoleacetic acid while still the major metabolite in blood was now only 1.4 times the concentration of imidazoleacetic acid. Additionally, the blood concentration of histamine during the infusion exceeded that of the metabolites. 4 t-Methylimidazoleacetic acid was also the principal metabolite in blood and tissues following histamine infusion into a cannula carrying a replacement venous blood supply to the liver of abdominally eviscerated cats. Imidazoleacetic acid and t-methylhistamine were present in equal concentrations and in one-quarter to one-third that of the methylated acid. The latter was also the principal metabolite following intra-arterial histamine infusion to abdominally eviscerated cats without a hepatic blood supply, although initially t-methylhistamine predominated: a large peak of histamine was present during the infusion period. When additionally the renal vessels were ligated, t-methylhistamine predominated throughout the experiment. 5 In conclusion, intraduodenally instilled histamine was metabolized equally by diamine oxidase and imidazole N-methyltransferase (followed by deamination by monoamine oxidase). In contrast, imidazole N-methyltransferase was the principal inactivator of parenterally infused histamine, deamination of t-methylhistamine by monoamine oxidase becoming progressively less efficient with the cumulative exclusion of the intestines, liver and kidney from the circulation.

[14C]‐β‐phenethylamine, its distribution after administration by various routes to cats, and the effects of monoamine oxidase inhibitors

“…Instillation ofphenethylamine into the small intestine The procedure was as described previously for histamine (Imrie et al, 1978). Briefly, drugs including ["4C]-PEA in 10 ml saline (0.9% w/v) were instilled via a cannula tied anterogradely into the duodenum; a more distal cannula, inserted retrogradely into the jejunum, allowed the lumen contents to be washed through and collected at the end of the experiments; this length of intestine weighed 40 ± 5 g. Blood was removed at 5 or O min intervals via scalp infusion needles (butterfly-23 0.6 mm, Abbott Ireland, Sligo, Eire), cemented with cyanoacrylate adhesive into the greater portal vein (PV) and cranial mesenteric artery (CMA), the needle tips disposed so that blood flow was uninterrupted.…”

“…Briefly, drugs including ["4C]-PEA in 10 ml saline (0.9% w/v) were instilled via a cannula tied anterogradely into the duodenum; a more distal cannula, inserted retrogradely into the jejunum, allowed the lumen contents to be washed through and collected at the end of the experiments; this length of intestine weighed 40 ± 5 g. Blood was removed at 5 or O min intervals via scalp infusion needles (butterfly-23 0.6 mm, Abbott Ireland, Sligo, Eire), cemented with cyanoacrylate adhesive into the greater portal vein (PV) and cranial mesenteric artery (CMA), the needle tips disposed so that blood flow was uninterrupted. A non-cannulated length of small intestine immediately distal to the second cannula was used to measure the uptake of 14C-compounds from arterial blood (Imrie et al, 1978). MAO inhibitors were given intraduodenally (i.d.)…”

“…Although less potent as a pressor agent than cats, revealed a dissimilar pattern of absorption, another dietary amine, tyramine, its ingestion in distribution and tissue concentrations compared to cheese could also have contributed in a minority ofthe tyramine. Indeed, since these tissue concentrations were substantially larger than those following identical doses of tyramine, P-phenethylamine emerges as potentially the most relevant to migraine of the three dietary amines examined, the others being histamine (Imrie et al, 1978) and tyramine (Garcha et al, 1983a). A preliminary account of the results has been communicated to the British Pharmacological Society (Garcha et al, 1983b).…”