The effects of alpha 1-adrenergic and muscarinic cholinergic stimulation on prostaglandin release by rabbit iris.
We have investigated the effects of norepinephrine (NE) and acetylcholine (ACh) on prostaglandin (PGE2 and 6 keto-PGF1 alpha) production by rabbit iris, measured by radioimmunoassay (RIA), and the type of phospholipase activated by NE in irides in which phosphatidylinositol (PI) was doubly prelabeled with [3H] myo-inositol and [1-14C] arachidonic acid (14C-AA), quantitated by radiometric and chromatographic methods. PGE2 output in 60 min (3.6 micrograms/g tissue) was 2.6 times greater than 6 keto-PGF1 alpha. PG production is time-dependent and it is stimulated by NE and ACh in a dose-dependent manner. The NE- and ACh-induced release of PGE2, measured by RIA, is mediated through alpha 1-adrenergic and muscarinic cholinergic receptors, respectively, and it requires Ca2+ for maximal stimulation. Studies on the mechanism of AA release from PI in irides doubly prelabeled with 14C-AA and [3H] myo-inositol revealed the following: (a) Both NE and ACh increased the breakdown of PI, and this was accompanied by a significant increase in the release of AA and consequently PGE2. The stimulatory effects of NE and ACh are mediated through alpha 1-adrenergic and muscarinic cholinergic receptors respectively. (b) The NE-induced formation of 3H-lyso PI and the NE-induced metabolism of 14C-1,2-diacyl-glycerol (DG) are time-dependent. Two pathways for AA release from PI are probably operative in the iris: (a) An indirect release by PI-specific phospholipase C which produces DG, followed by the actions of DG- and monoacylglycerol lipases on DG to release AA. (b) A direct release by phospholipase A2. Whether lyso PI is a product of the polyphosphoinositide response remains to be established. Other phospholipids such as phosphatidylcholine and phosphatidylethanolamine could also serve as a source for AA in PG synthesis. In conclusion, the data presented provide evidence that in the iris the neuro-transmitter-stimulated release of PG and AA, from phosphoinositides, for PG synthesis is coupled to the activation of alpha 1-adrenergic and muscarinic cholinergic receptors.
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis*; D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001285:Atropine / Q000494:pharmacology*; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D015232:Dinoprostone; D005260:Female; D007294:Inositol / Q000378:metabolism; D007498:Iris / Q000187:drug effects / Q000378:metabolism*; D007700:Kinetics; D008297:Male; D008861:Microsomes / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D011224:Prazosin / Q000494:pharmacology*; D011458:Prostaglandins E / Q000096:biosynthesis*; D011799:Quinazolines / Q000494:pharmacology*; D011817:Rabbits; D014403:Tubocurarine / Q000494:pharmacology; D015016:Yohimbine / Q000494:pharmacology*
D001095:Arachidonic Acids; D011458:Prostaglandins E; D011799:Quinazolines; D016718:Arachidonic Acid; D015016:Yohimbine; D000001:Calcimycin; D007294:Inositol; D015121:6-Ketoprostaglandin F1 alpha; D001285:Atropine; D015232:Dinoprostone; D000109:Acetylcholine; D002118:Calcium; D014403:Tubocurarine; D009638:Norepinephrine; D011224:Prazosin