[quote:20dfca3312="matchupeabody"]In all of Dr. Sears’s books, he clearly states that “good” eicosanoids cause vasodilation, inhibit cellular proliferation, etc. and “bad” eico.’s do the opposite. He also states, though, in “Omega Rx Zone” (p. 235) that what differentiates a “good” from a “bad” is the second messengers they produce (“good” = cAMP; “bad” = IP3 / DAG). Unless I am mistaken, he never links these two concepts. So, my question to any zoner who knows the answer: Is the physiological effect of an eicosanoid (e.g. PGE1 and vasodilation) independent of its ability to produce certain second messengers? Or is it, in fact, the increase in the second messenger (cAMP) that causes the effect (vasodilation)?[/quote:20dfca3312]
The vasodilation properties of PGE1 are attributed to its ability to raise cAMP levels. (1) (2). The vasodilation resulting from increasing cAMP levels is believed to be due to its ability to decrease intracellular calcium (3) which results in the relaxation of smooth muscle. The secondary messenger IP3 does the the opposite. It promotes increases in Ca++ levels which results in smooth muscle contraction. (4). The opposing secondary messenger systems also regulate the hydrolysis of glycogen to glucose (cAMP) and synthesizing glycogen from glucose (IP3) (5).
(1) Kadowitz PJ, et al [i:20dfca3312]"Influence of Prostaglandin E1 and F2alpha on pulmonary vascular resistance, isolated lobar vessels and cyclic nucleotide levels"[/i:20dfca3312] J Pharmacol Exp Ther 1975 Mar; 192(3):677-87
(2) Naka Y, et al [i:20dfca3312]"cAMP-mediated vascular protection in an orthotopic rat lung transplant model. Insights into the mechanism of action of Prostaglandin E1 to improve lung preservation"[/i:20dfca3312] Circ Res 1996 Oct;79(4):773-83
(3) McDaniel NL, et al [i:20dfca3312] "Cyclic AMP relaxes swine arterial smooth muscle predominantly by decreasing cell Ca2+ concentration"[/i:20dfca3312] J Physiology 1991 Aug;439:147-160
(4) Benoit, JN, et al [i:20dfca3312]"Vascular reactivity following ischemia/reperfusion"[/i:20dfca3312] Frontiers in Bioscience 1997 May 15;2:e28-33
(5) Peter Raven and Geroge Johnson [i:20dfca3312]Biology Sixth Edition [/i:20dfca3312]2002 McGraw Hill, New York, NY