Antagonistic effect of amiloride on alpha-2 adrenoceptor-mediated pigment aggregation: pharmacological heterogeneity between B-HT 920 and noradrenaline.
Pigment aggregation in melanophores from the cuckoo wrasse (Labrus ossifagus L.) has previously been shown to be mediated by alpha-2 adrenoceptors. In the present investigation, the effect of amiloride on pigment aggregation induced by noradrenaline and B-HT 920 was studied. Amiloride caused a parallel shift to the right in concentration-response curves for 5-allyl-2-amino-5,6,7,8-tetrahydrothiazolo-[4,5-d]azepine-dihyd roc hloride: (B-HT 920), with no change in the maximal response, indicating simple competitive inhibition. Subsequent Schild plot analysis gave a straight line with a slope of almost unity (0.95) and a KB of 5 x 10(-6) M. In contrast to the effect of amiloride on B-HT 920-induced pigment aggregation, only a very high concentration of amiloride (1 x 10(3) M) inhibited the corresponding effect of noradrenaline. Na+/H+ exchange has been suggested as a possible mechanism for alpha-2 adrenoceptors, and the amiloride analogs 5-(N,N-dimethyl)amiloride and 5-(N,N-hexamethylene)amiloride are known to be more specific than amiloride itself in this respect. However, these analogs inhibited the effect of B-HT 920 significantly less effectively than amiloride. Furthermore, manipulating the extracellular pH between 6.8 and 7.8 did not affect the concentration response curves of B-HT 920. Neither did the prostanoid pathway inhibitors, quinacrine or indomethacin, inhibit the pigment-aggregating effect of B-HT 920. The present results suggest that amiloride competes with B-HT 920 as receptor antagonist, and that Na+/H+ exchange is insignificant for the alpha-2 adrenoceptor-stimulated pigment aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, Linköping University, Sweden.
S P
SP
Svensson
L G
LG
Mårtensson
N
N
Grundström
R G
RG
Andersson
E J
EJ
Cragoe
J O
JO
Karlsson
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D001381:Azepines / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology; D005399:Fishes; D009638:Norepinephrine / Q000494:pharmacology*; D010860:Pigments, Biological / Q000378:metabolism*; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects* / Q000502:physiology; D012964:Sodium / Q000378:metabolism
D000316:Adrenergic alpha-Agonists; D001381:Azepines; D010860:Pigments, Biological; D011942:Receptors, Adrenergic, alpha; C057360:5-(N,N-hexamethylene)amiloride; C039465:5-dimethylamiloride; C024763:talipexole; D000584:Amiloride; D012964:Sodium; D000242:Cyclic AMP; D009638:Norepinephrine