Identification of a presynaptic cannabinoid CB1 receptor in the guinea-pig atrium and sequencing of the guinea-pig CB1 receptor.

We studied whether cannabinoid CB(1) receptors occur on the sympathetic neurones innervating the guinea-pig atrium and renal cortex. Atrial and cortical kidney pieces preincubated with [(3)H]-noradrenaline were superfused and the electrically (3 Hz)-evoked tritium overflow was examined. The evoked overflow in atrium was inhibited by the cannabinoid agonist WIN 55,212-2 maximally by 35%; its concentration-response curve was shifted to the right by the CB(1) antagonist rimonabant (pA(2) 8.3), which, by itself, did not affect the evoked overflow. The evoked overflow in the renal cortex was not altered by WIN 55,212-2. The muscarinic agonist oxotremorine and prostaglandin E(2) inhibited the evoked overflow maximally by 55 and 65% in atrium and by 80 and 55% in kidney, respectively. Furthermore, the nucleotide sequence of the guinea-pig CB(1) receptor was determined (GenBank DQ355990). The deduced amino acid sequence has a high homology to the corresponding sequence of man (98.7%) and rat or mouse (99.2%). In conclusion, presynaptic CB(1) receptors leading to inhibition of noradrenaline release occur in guinea-pig atrium but not renal cortex. The deduced amino acid sequence of the guinea-pig CB(1) receptor shows a homology of 99% to the CB(1) receptor sequence of rodents and humans.