title: Histamine H(2) -like receptors in chick cerebral cortex: effects on cyclic AMP synthesis and characterization by [(3) H]tiotidine binding.
abstract: In this study, histamine (HA) receptors in chick cerebral cortex were characterized using two approaches: (1) analysis of the effects of HA-ergic drugs on the cAMP-generating system, and (2) radioreceptor binding of [(3) H]tiotidine, a selective H(2) antagonist. HA was a weak activator of adenylyl cyclase in a crude membrane preparation of chick cerebrum. On the other hand, HA (0.1-1000 microm) potently and concentration dependently stimulated cAMP production in [(3) H]adenine pre-labelled slices of chick cerebral cortex, displaying an EC(50) value (concentration that produces 50% of maximum response) of 2.65 microm. The effect of HA was mimicked by agonists of HA receptors with the following rank order of potency: HA >or= 4-methylHA (H(2)) >or= N alpha,N alpha-dimethylHA (H(3) >> H(2) = H(1)) >> 2-methylHA (H(1)) >> 2-thiazolylethylamine (H(1)) >or= R alpha-methylHA (H(3)) >> amthamine, dimaprit (H(2)), immepip (H(3), H(4)). The HA-evoked increase in cAMP production in chick cerebral cortex was antagonized by selective H(2) receptor blockers (aminopotentidine >or= tiotidine > ranitidine >> zolantidine), and not significantly affected by mepyramine and thioperamide, selective H(1) and H(3) /H(4) receptor blockers, respectively. A detailed analysis of the antagonistic action of aminopotentidine (vs. HA) revealed a non-competitive mode of action. The binding of [(3) H]tiotidine to chick cortical membranes was rapid, stable and reversible. Saturation analysis resulted in a linear Scatchard plot, suggesting binding to a single class of receptor binding site with high affinity [equilibrium dissociation constant (K (d)) = 4.42 nm] and high capacity [maximum number of binding sites (B (max) ) = 362 fmol/mg protein]. The relative rank order of HA-ergic drugs to inhibit [(3) H]tiotidine binding to chick cerebrum was: antagonists - tiotidine >> aminopotentidine = ranitidine >or= zolantadine >> thioperamide - triprolidine; agonists - HA >or= 4-methylHA >> 2-methylHA >or=R alpha-methylHA - dimaprit. In conclusion, chick cerebral cortex contains H(2) -like HA receptors that are linked to the cAMP-generating system and are labelled with [(3) H]tiotidine. The pharmacological profile of these receptors is different from that described for their mammalian counterpart. It is suggested that the studied receptors represent either an avian-specific H(2) -like HA receptors or a novel subtype of HA receptors.
authors.affiliation: Department of Biogenic Amines, Polish Academy of Sciences, Lodz, Poland. jolantaz@amina1.zabpan.lodz.pl
authors.forename: Jolanta B
authors.initials: JB
authors.lastname: Zawilska
authors.forename: Agata
authors.initials: A
authors.lastname: Woldan-Tambor
authors.forename: Jerzy Z
authors.initials: JZ
authors.lastname: Nowak
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D001665:Binding Sites / Q000187:drug effects; D001667:Binding, Competitive / Q000187:drug effects; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002645:Chickens; D002927:Cimetidine / Q000031:analogs & derivatives* / Q000493:pharmacokinetics*; D000242:Cyclic AMP / Q000096:biosynthesis*; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology; D017442:Histamine Agonists / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D008297:Male; D011869:Radioligand Assay; D011969:Receptors, Histamine H1 / Q000187:drug effects; D011970:Receptors, Histamine H2 / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D018100:Receptors, Histamine H3 / Q000187:drug effects
chemical_list: D017442:Histamine Agonists; D006633:Histamine Antagonists; D011969:Receptors, Histamine H1; D011970:Receptors, Histamine H2; D018100:Receptors, Histamine H3; D002927:Cimetidine; D006632:Histamine; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; C023990:tiotidine