Histamine H-2 receptor stimulation and inhibition of pepsin secretion in the dog.
Although low doses of histamine (less than 150 nM/kg.hr) stimulate pepsin secretion, higher doses inhibit pepsin secretion in a dose-dependent manner. To better histamine stimulation of pepsin, histamine was used at doses at the lower end of the dose-response scale in five dogs with gastric fistula. Five doses of histamine below the ED50 for acid, viz, 9, 22.5, 67.5, 90 and 112 nM/kg.hr in 45-min steps, provided values for pepsin secretion from which Ed50 = 11.4 nmol/kg.hr (i.e., about 1/12 the ED50 for acid) and calculated maximum 22,600 peptic U/30 min were calculated. To document the inhibition, pepsin secretion was first stimulated by an infusion of bethanechol (0.4 mumol/kg.hr). A super-added injection of the histamine H-2 agonist 4-methylhistamine (0.4 or 0.8 mumol/kg) produced strong additional acid stimulation and immediate 40% suppression of pepsin secretion. The ratio pepsin/acid was reduced to one-third of control for the 90 min after 4-methylhistamine. The most specific H-2 agonist impromidine had the same effects, whereas pentagastrin (1.95 nmol/kg) inhibited both acid and pepsin secretion stimulated by bethanechol. The specificity of H-2 effect of impromidine was confirmed by simultaneous tachycardia and hypotension; pentagastrin did not produce cardiovascular effects. These studies confirm the unique effect of histamine on the peptic cell of the dog in which both stimulation and inhibition are H-2 receptor-mediated effects.
D000818:Animals; D004285:Dogs; D005750:Gastric Juice / Q000378:metabolism; D005753:Gastric Mucosa / Q000187:drug effects / Q000378:metabolism; D006146:Guanidines / Q000494:pharmacology; D006632:Histamine / Q000494:pharmacology; D007093:Imidazoles / Q000494:pharmacology; D017446:Impromidine; D008761:Methylhistamines / Q000494:pharmacology; D010434:Pepsin A / Q000378:metabolism*; D011968:Receptors, Histamine / Q000187:drug effects*; D011970:Receptors, Histamine H2 / Q000187:drug effects*
D006146:Guanidines; D007093:Imidazoles; D008761:Methylhistamines; D011968:Receptors, Histamine; D011970:Receptors, Histamine H2; C025566:4-methylhistamine; D006632:Histamine; D017446:Impromidine; D010434:Pepsin A