Abstract
Purpose::
Obestatin is an amidated 23-amino acid peptide, part of the ghrelin precursor, which was found to bind specifically to GPR 39. Interestingly, these two peptides appear to have opposite effects. Obestatin decreases the contractile activity of jejunal muscle strips and antagonized the stimulatory effect of ghrelin. Previously our group had demonstrated that ghrelin relaxes the carbachol precontracted iris sphincter muscle, through an independent GHSR1a pathway that promotes the release of prostaglandins. This study investigates the effect of obestatin in the contraction of the iris sphincter muscle.
Methods::
Rabbit iris sphincter muscles (n=22) were dissected and attached to a force transducer, on a horizontal organ bath containing a modified Krebs-Ringer solution (1.8 mM Ca2+; 35ºC). The effects of obestatin were evaluated on the resting tension of the muscle in a dose-response curve (10-9 - 10-5M; n=8). In a second protocol the effects of obestatin were evaluated in two consecutive contractions elicited by carbachol (10-6M; n=8) and compared to two consecutive control contractions (n=6), in the presence of the vehicle. Only significant results (mean±SE, p<0.05) are given, expressed as % changes from control.
Results::
Obestatin did not alter the resting tension of the iris sphincter muscle. Carbachol increased active tension from 0.5±0.04 mN to 1.48±0.08 mN. In two consecutive contractions obestatin increased the second carbachol elicited contraction in19.6±9.4%, while in its absence the second contraction was decreased in 11.4±4.3% when compared to the first.
Conclusions::
Obestatin potentiates the carbachol elicited contraction of the iris sphincter muscle. Similarly to what was described in jejunal strips muscles, in the iris sphincter muscle, obestatin appears to have an opposite effect of that described to Ghrelin.
Keywords: iris • neuropeptides • signal transduction: pharmacology/physiology