High efficiency coupling of alpha-1 adrenergic receptors to inositol phospholipid metabolism revealed by denervation of rat vas deferens.

The effect of surgical denervation on alpha-1 adrenergic receptor-stimulated inositol phosphate (IP) formation was examined in rat vas deferens. Rings of tissue from acutely reserpinized animals were incubated with [3H]inositol in the presence of lithium to block IP degradation and desmethylimipramine to block neuronal uptake of norepinephrine. Eighteen days after denervation the potency of norepinephrine in stimulating [3H]IP accumulation was increased 10-fold. The potency of epinephrine was increased only 3.5-fold, and the potency of phenylephrine was not altered significantly. The potency of norepinephrine in control tissues incubated with 0.1 microM desmethylimipramine was unaffected by addition of cocaine to further block neuronal uptake; however, addition of pyrogallol and pargyline to block metabolic degradation increased the potency of norepinephrine in these tissues by 6-fold. Two days after denervation there was a similar 5-fold increase in the potency of norepinephrine. In denervated tissues, the potency of norepinephrine in stimulating [3H]IP accumulation was decreased about 40-fold after receptor inactivation with 1 microM phenoxybenzamine. These results suggest that there is a substantial alpha-1 adrenergic receptor reserve for stimulating [3H]IP accumulation in rat vas deferens which is normally obscured by rapid inactivation of norepinephrine. The increase in the potency of norepinephrine after denervation appears to be due to removal of these inactivation mechanisms.