Related Experiment Videos
Mechanisms mediating substance P-induced contraction in the rat iris in vitro
A Grumann-Júnior1, M A Dias, R V Alves
1Department of Pharmcology, Centre of Biological Sciences, Universidade Federal de Santa Catarina, Florianópolis, Brazil.
Purpose:
To determine some of the mechanisms by which substance P (SP) induces contraction in the isolated rat iris.
Methods:
Rings of rat iris were mounted in a 5-ml organ chamber containing Krebs solution at 37 degrees C under basal tension of 75 mg, and isometric tension was recorded.
Results:
Substance P produced graded contraction in the rat iris, being approximately 40-fold more potent than carbachol. Peptidase inhibitors (captopril, phosphoramidon, thiorphan) did not affect the SP response. The SP contraction was dependent on external Ca2+ by a mechanism resistant to both nifedipine and omega-conotoxin GVIA. Atropine and tetrodotoxin significantly shifted the SP response to the right (three- and fivefold, respectively). Neither phorbol nor genistein altered the SP-induced contraction, whereas staurosporine caused a weak inhibition. Indomethacin, pyrilamine, guanethidine, 8-37 calcitonin gene-related peptide (CGRP) fragment, and NG-nitro-L-arginine methyl ester had no effect on SP response. All the natural tachykinin agonists caused concentration-dependent contraction in rat iris with similar maximal responses. The NK3 selective agonist senktide caused graded contraction, being approximately 150-fold more active than the NK2 selective agonist [beta-ala] NKA. The NK1 selective agonist SP methyl ester induced a small contraction. The NK3 and NK2 antagonists SR 142801 and SR 48968 shifted the SP response to the right. Schilds plots gave pA2 (negative logarithm of the molar concentration of antagonist causing a twofold rightward displacement of the concentration response curves) values of 9.37 and 7.97 and slopes of 0.70 and 1.02, respectively.
Conclusions:
Substance P produces a potent contraction in the isolated rat iris that seems to depend on the neural release of acetylcholine by tetrodotoxin-sensitive mechanisms. Its response relies largely on external Ca2+, through mechanisms independent of activation of L- or N-type Ca2+ channels, and is probably mediated via activation of NK3 and NK2 receptors.