title: Development of an assay for H2-receptor antagonists using isolated fat cells.
abstract: Fat cells were isolated by collagenase digestion of adipose tissue from male dogs. The cells were shown to be responsive to both histamine and norepinephrine in producing glycerol, a marker for lipolysis. The histamine-stimulated response was shown to be mediated by H2-receptors because it was inhibited by the H2-receptor antagonists metiamide and cimetidine, but not by H1 blockers such as tripelennamine, or by other agents such as propranolol. Conversely, norepinephrine-stimulated lipolysis was inhibited by propranolol but not by metiamide. The KD estimated for cimetidine and metiamide was approximately 10(-6) M, which compares favorably with that observed in other H2-receptor systems. The relative potency of various histamine H2-receptor agonists in this system was comparable to that seen in other H2-receptor systems. This assay has the advantage of utilizing a homogeneous cell preparation and is not complicated by tachyphylaxis. The dogs which are the source of the adipose tissue can potentially be used for other studies after a suitable recovery period. This system appears useful in screening novel compounds for H2-receptor antagonist or agonist activity.
mesh_terms: D000273:Adipose Tissue / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D000818:Animals; D003584:Cytological Techniques; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D005260:Female; D005990:Glycerol / Q000378:metabolism; D006632:Histamine / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology*; D050356:Lipid Metabolism; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D011817:Rabbits; D051381:Rats; D013045:Species Specificity
chemical_list: D006635:Histamine H2 Antagonists; D006632:Histamine; D005990:Glycerol; D009638:Norepinephrine