EVIDENCE FOR A CANNABINOID RECEPTOR IN SEA-URCHIN SPERM AND ITS ROLE IN BLOCKADE OF THE ACROSOME REACTION

被引:89
作者
CHANG, MC
BERKERY, D
SCHUEL, R
LAYCHOCK, SG
ZIMMERMAN, AM
ZIMMERMAN, S
SCHUEL, H
机构
[1] SUNY BUFFALO,SCH MED & BIOMED SCI,DEPT ANAT SCI,BUFFALO,NY 14214
[2] SUNY BUFFALO,SCH MED & BIOMED SCI,DEPT PHARMACOL & THERAPEUT,BUFFALO,NY 14214
[3] UNIV TORONTO,DEPT ZOOL,TORONTO M5S 1A1,ONTARIO,CANADA
[4] YORK UNIV,GLENDON COLL,DIV NAT SCI,N YORK M3J 1P3,ONTARIO,CANADA
关键词
FERTILIZATION; SPERM; ACROSOME REACTION; MARIJUANA; DELTA-9-TETRAHYDROCANNABINOL; CP-55,940; CANNABINOID RECEPTOR; MODULATE RESPONSE TO STIMULATION;
D O I
10.1002/mrd.1080360416
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Delta-9-tetrahydrocannabinol ((-)DELTA9 THC), the primary psychoactive cannabinoid in marihuana, reduces the fertilizing capacity of sea urchin sperm by blocking the acrosome reaction that normally is stimulated by a specific ligand in the egg's jelly coat. The bicyclic synthetic cannabinoid [H-3]CP-55,940 has been used as a ligand to demonstrate the presence of a cannabinoid receptor in mammalian brain. We now report that [H-3]CP-55,940 binds to live sea urchin (Strongylocentrotus purpuratus) sperm in a concentration, sperm density, and time-dependent manner. Specific binding of [H-3]CP-55,940 to sperm, defined as total binding displaced by (-)DELTA9THC, was saturable: K(D) 5.16 +/- 1.02 nM; Hill coefficient 0.98 +/- 0.004. This suggests a single class of receptor sites and the absence of significant cooperative interactions. Sea urchin sperm contain 712 +/- 122 cannabinoid receptors per cell. Binding of [H-3]CP-55,940 to sperm was reduced in a dose-dependent manner by increasing concentrations of CP-55,940, (-)DELTA9THC, and (+)DELTA9THC. The rank order of potency to inhibit binding of [H-3]CP-55,940 to sperm and to block the egg jelly stimulated acrosome reaction was: CP-55,940 > (-)DELTA9THC > (+)DELTA9THC. These findings show that sea urchin sperm contain a stereospecific cannabinoid receptor that may play a role in inhibition of the acrosome reaction. The radioligand binding data obtained with live sea urchin sperm are remarkably similar to those previously published by other investigators using [H-3]CP-55,940 on mammalian brain and nonneural tissues. The cannabinoid binding properties of this receptor appear to have been highly conserved during evolution. We postulate that the cannabinoid receptor may modulate cellular responses to stimulation. (C) 1993 Wiley-Liss, Inc.
引用
收藏
页码:507 / 516
页数:10
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