1,721,274 research outputs found
Effect of selective antagonist cannabinoid CB1 receptors on a bovine iridial circular muscle
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Functional characterization of vasorelaxant responses to cannabinoid agonists in bovine ophthalmic arteries
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Epigallocatechi-3-gallate relaxes the isolated bovine ophthalmic artery: involvement of phosphoinositide 3-kinase-Akt-nitric oxide/cGMP signalling pathway
No full textThe present study investigates the direct action and the underlying mechanism(s) of epigallocatechin-3-
gallate (EGCG) vasomotor effects on the bovine isolated ophthalmic artery. Adjacent rings were cut from
each artery and mounted in a wire miograph system for isometric recording. Concentration–response curves
for EGCG were constructed by adding cumulative concentrations of the drug to arterial rings pre-contracted
with 5-HT (1 μM). Effects of mechanical endothelial cell removal and of selective blockers of the nitric oxide
(NO)/cGMP pathways were investigated on the EGCG relaxant responses. EGCG relaxed ophthalmic arteries
and maximum relaxation was 78.4±2.64%. Mechanical removal of endothelium, blockade of soluble
guanylyl cyclase by 1H-1,2,4-oxadiazolo [4,3-a]quinoxalin-1-one (ODQ, 1 and 5 μM) or inhibition of nitric
oxide (NO) synthase by NG-nitro-L-arginine (L-NAME, 50 and 100 μM) reduced significantly the relaxant
response to catechin; moreover, the NO donor S-nitroso-N-acetylpenicillamine (SNAP, 100 μM) significantly
increased the vasorelaxant responses to EGCG. Relaxation to EGCG was inhibited by iberiotoxin (200 nM), a
blocker of big-conductance Ca2+-activated K+ (BKCa) channel, whereas the blockade of KATP channel by
glibenclamide (5 μM) and of small-conductance Ca2+-activated K+ (SKCa) channel by apamin (100 nM)
elicited no effect. Interestingly, also inhibition of phosphoinositide-3-kinase (PI3K) by wortmannin (100 nM)
and of Akt by SH6 (1 μM) markedly decreased the EGCG-evoked vasorelaxation. These data suggest that
EGCG induced vasorelaxation in ophthalmic arteries with endothelium-intact via the activation of the NO/
cGMP signalling pathway and defined an intriguing role for PI3K and Akt as upstream mediators for
activation of NO-mediated relaxant responses
Pharmacological characterization of the 5-HT1A, 5-HT2 and 5-HT3 receptors in the bovine ciliary muscle
No full textWe aimed to investigate the effects of serotonin (5-hydroxytryptamine, 5-HT) on the bovine ciliary muscle and subsequently to characterize and identify the subtypes of 5-HT receptors involved in the serotonin-evoked contractility muscle. The binding of [3H]ketanserin, [3H]granisetron and [3H]8-hydroxy-2-(di-n-propylamino)tetralin ([3H]8-OH-DPAT) was analyzed. All labelled compounds bound with high affinity to a single site in the membrane preparations studied. The affinity (Kd) of the binding site was 7.5±1.2 nM for [3H]ketanserin, 6.9±0.8 nM for [3H]granisetron and 4.4±0.31 nM for [3H]8-OH-DPAT. The density of receptors (Bmax) was 1062±43.0 fmol/mg protein for [3H]ketanserin, 566±2.32 fmol/mg protein for [3H]granisetron and 205±4.63 fmol/mg protein for [3H]8-OH-DPAT. The serotonin-induced contraction appeared to be competitively antagonized by ketanserin (0.1, 1 and 10 μM) and ondansetron (0.1, 10 and 100 μM) which produced a pA2 value of 8.5±0.12 and 8.0±0.19, respectively. 8-OH-DPAT and 5-carboxamidotryptamine (5-CT) proved to be completely ineffective. We conclude that serotonin induces bovine ciliary muscle contraction via 5-HT2 and 5-HT3 receptors while the 5-HT1A receptors, although present, do not mediate the contractile response
Signaling cross-talk between cannabinoid and muscarinic systems actives Rho-kinase and increases the contractile responses of the bovine ciliary muscle
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Evidences for the Involvement of Cannabinoid CB1 Receptors in the Bimatoprost-Induced Contractions on the Human Isolated Ciliary Muscle
No full textPURPOSE. To evaluate the bimatoprost effects in the isolated
human ciliary muscle and to assess how these response can be
modulated by AL8810 and SR141716A.
METHODS. In a myograph system (isometric force measurement),
ciliary muscles were exposed cumulatively to PGF2,
latanoprost, travoprost, bimatoprost, and anandamide (0.1
nM-10 M). Experiments were also conducted in the presence
of AL8810 (FP receptor antagonist; 100 nM) or SR141716A
(CB1 receptor antagonist; 10–100 nM). Contractions were expressed
as the percentage of 10 M carbachol-induced contractions.
RESULTS. In quiescent tissues, concentration-response curves
for bimatoprost, anandamide, PGF2, latanoprost, and travoprost
were constructed. Bimatoprost showed an important
contractile effect on isolated human ciliary muscle strips
(Emax 125% 0.09%); the maximal effect was higher than
that obtained with carbachol. Contractions were inhibited by
SR141716A (10 and 100 nM) and AL8810 (100 nM).
CONCLUSIONS. This study showed evidence of direct interaction
of bimatoprost with the contractility of the human ciliary
muscle through interaction with cannabinoid CB1 receptor and
prostanoid FP receptors
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