Evidence for the lack of interaction between (+/-)-1-O-octadecyl-2-acetylglyceryl-3-phosphorylcholine and alpha-adrenoceptors in vivo and in vitro.

The interactions of (+/-)-1-O-octadecyl-2-acetylglyceryl-3-phosphorylcholine (octadecyl-AGPC) with alpha-adrenoceptors were studied in rat mesenteric artery, cat nictitating membrane and on the blood pressure of the cat and spontaneously hypertensive (SH) rat. Using a direct radioligand alpha-adrenoceptor binding assay in particulate fractions of rat mesenteric arteries, octadecyl-AGPC was found to be 5 X 10(7) and 75 times less potent than prazosin and noradrenaline (NA), respectively, in displacing (2,6-dimethoxyphenoxyethyl)-aminomethyl-1,4-benzodioxane ([3H]-WB 4101--a selective probe for the identification of alpha-adrenoceptors). In the cat, intravenous infusions of octadecyl-AGPC, which produce a hypotensive response, did not attenuate nictitating membrane contractions in vivo in response to intravenous injections of NA, adrenaline (Ad) or to electrical stimulation of the postganglionic fibres of the superior cervical ganglion. In these experiments, the pressor responses to NA or Ad were not affected by octadecyl-AGPC. Phentolamine, on the other hand, attenuated nictitating membrane contractions and blood pressure responses to Ad or NA. In the SH rat, octadecyl-AGPC decreased mean arterial blood pressure (MABP). After an intravenous dose of phentolamine which lowered MABP, the depressor response to octadecyl-AGPC was reduced. When MABP in the phentolamine-treated SH rat was restored to its initial level with an infusion of angiotensin II (AII), the depressor response to octadecyl-AGPC was restored to its original magnitude. The effectiveness of alpha-adrenoceptor blockade under these experimental conditions was monitored with intravenous NA and Ad. Thus, based on radioligand binding studies and pharmacological studies, it is concluded that octadecyl-AGPC lacks the ability to interact with alpha-adrenoceptors.