Abstract
Abstract: :
There is evidence that histamine can inhibit sympathetically-induced papillary dilation in cats by activation of H3-receptors (Koss and Hey, Naunyn-Schmiedeberg’s Arch. Pharmacol. 348: 141, 1993). It is, however, unclear whether this action is due to a direct effect of histamine on norepinephrine (NE) release from this tissue. Purpose: The aim of the present study was two-fold: (a) to examine the effect of exogenous histamine on NE release from bovine and human irides and (b) to classify the subtype of histamine receptors mediating this response in bovine irides. Methods: Isolated bovine and human irides were incubated in oxygenated Krebs solution containing 1.6 µM [3H]NE, and flurbiprofen (3 µM) for 1 hour. After incubation, tissues were prepared for studies of [3H]NE release using the superfusion method. Release of [3H]NE was elicited by 300 direct current pulses (supramaximal voltage, 2 ms pulse duration, 5 Hz) applied 84 minutes (S1) and 108 minutes (S2) after the onset of superfusion. Results: Histamine and other receptor selective agonists, R-α-methylhistamine (H3-) and imetit (H3-/H4-) caused a concentration-dependent inhibition of field-stimulated [3H]NE release from isolated bovine irides with the following rank order of potency: imetit ≷≷ R-α-methylhistamine ≷ histamine. All three agonist displayed a similar efficacy in inhibiting evoked [3H]NE release. An equimolar concentration of R-α-methylhistamine (1 µM) caused a similar degree of inhibition (35%) of electrically-induced [3H]NE release in both human and bovine irides. The inhibitory response produced by imetit (1 nM) was completely blocked by thioperamide (30 nM; H3-/H4-antagonist). Likewise, the inhibition caused by R-α-methylhistamine (1 µM) was abolished by clobenpropit (1 nM; H3-antagonist). Conclusion: We conclude that histamine can inhibit field stimulated [3H]NE release from isolated bovine and human irides. Furthermore, both prejunctional H3- and H4-receptors exist on sympathetic nerve terminals in the bovine irides. These heteroreceptors play an inhibitory role in the regulation of NE release from mammalian irides.
Keywords: 514 pharmacology • 447 iris • 541 receptors: pharmacology/physiology