A study of the H2-receptor for histamine stimulating adenylate cyclase in homogenates of guinea-pig lung parenchyma.
The effect of forskolin and several H2-agonists was investigated on the activity of adenylate cyclase in homogenates of guinea-pig lung parenchyma. Histamine, 0.1 microM to 1 mM, dimaprit, 1 microM to 10 mM, 4-methyl histamine, 0.1 microM to 10 mM, impromidine, 10 nM to 10 microM and forskolin, 1 nM to 100 microM, all produced a dose-dependent stimulation of adenylate cyclase activity above the basal level. The histamine H1-receptor antagonist mepyramine, 10 microM, and beta-adrenoceptor antagonist propranolol, 10 microM, had no effect on the stimulation by histamine of adenylate cyclase. The dose-response curve for stimulation by histamine of adenylate cyclase was shifted to the right in a dose-dependent manner by increasing concentrations of several H2-antagonists. Schild plots constructed for each H2-antagonist produced straight lines with slopes not significantly different from unity. The equilibrium dissociation constants obtained for the H2-antagonists in this study were similar to those previously reported for inhibition of dimaprit-induced relaxation of the pre-contracted lung strip, inhibition of [3H]-tiotidine binding to homogenates of guinea-pig lung parenchyma and inhibition of histamine-stimulated adenylate cyclase in guinea-pig gastric mucosa.
Foreman
J C
JC
Norris
D B
DB
Rising
T J
TJ
Webber
S E
SE
D000262:Adenylyl Cyclases / Q000032:analysis*; D000818:Animals; D002927:Cimetidine / Q000031:analogs & derivatives / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006632:Histamine / Q000494:pharmacology*; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008168:Lung / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D011433:Propranolol / Q000494:pharmacology; D011738:Pyrilamine / Q000494:pharmacology; D011968:Receptors, Histamine / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects*
D006635:Histamine H2 Antagonists; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; D005576:Colforsin; D002927:Cimetidine; D006632:Histamine; D011433:Propranolol; D000262:Adenylyl Cyclases; C023990:tiotidine; D011738:Pyrilamine