Finding of the endocannabinoid signalling system in Hydra, a very primitive organism: Possible role in the feeding response

Hydra (Cnidaria) is the first animal organism to have developed a neural ne twork, which has been proposed to control, inter alia, the "feeding respons e", i.e. a mechanism through which the coelenterate opens and then closes i ts mouth in the presence of prey and/or glutathione. Here, we report that H ydra contains: (i) selective cannabinoid binding sites; (ii) the endogenous cannabinoid receptor ligand, anandamide (arachidonoylethanolamide); (iii) a fatty acid amide hydrolase-like activity catalysing anandamide hydrolysis ; and (iv) the putative biosynthetic precursor of anandamide, N-arachidonoy lphos-phatidylethanolamine. We suggest that this "endogenous cannabinoid sy stem" is involved in the modulation of the "feeding response". Anandamide ( 1 nM-1 mu M) potently inhibited (up to 45%) the glutathione-induced "feedin g response" by accelerating Hydra vulgaris mouth closure. The effect was ma ximal at 100 nM anandamide and was reversed by the selective antagonist of the CB1 subtype of mammalian cannabinoid receptors, SR 141716A (50-100 nM). Specific cannabinoid binding sites were detected in membranes from Hydra p olyps by using [H-3]SR 141716A (K-d= 1.87 nM, B-max = 26.7 fmol/mg protein) , and increasing anandamide concentrations were found to displace the bindi ng of [3H]SR 141716A to these membranes (K-i= 505 nM). Hydra polyps were al so found to contain amounts of anandamide (15.6 pmol/g) and N-arachidonoylp hosphatidylethanolamine (32.4 pmol/g), as well as the other "endocannabinoi d" 2-arachidonoylglycerol (11.2 nmol/g), comparable to those described prev iously for mammalian brain. Finally, a fatty acid amide hydrolase activity (V-max = 3.4 nmol/min/mg protein), with subcellular distribution, pH depend ency and sensitivity to inhibitors similar to those reported for the mammal ian enzyme, but with a lower affinity for anandamide (K-m= 400 mu M), was a lso detected in Hydra polyps. These data suggest that the endocannabinoid s ignalling system plays a physiological role in Hydra that is to control the feeding response. Hydra is the simplest living organism described so far t o use this recently discovered regulatory system. (C) 1999 IBRO. Published by Elsevier Science Ltd.