CHOLINERGIC REGULATION OF THE RAT ADRENAL ZONA GLOMERULOSA

Using histochemical and immunocytochemical methods, cholinergic nerve fibres were demonstrated in the rat adrenal cortex, primarily in the c apsule and zona glomerulosa, and in the medulla. Some terminated among the glomerulosa cells or around blood vessels. Occasional fibres were also seen in the fasciculata, ending in islets of chromaffin tissue w ithout ramifications on cortical cells. To clarify the role of choline rgic innervation, a microvolume perifusion system was used to study st eroid production by the rat adrenal capsule-glomerulosa. Acetylcholine (ACh) itself had no reproducible effects; however, since variable amo unts of endogenous ACh were present, the actions of antagonists were a lso studied. The M-1 muscarinic receptor antagonist pirenzepine (10 an d 100 mu M) Stimulated aldosterone secretion. This stimulation was abo lished by co-incubation with carbachol, the M-1 agonist McN A-343 and by atropine. We found that the action of pirenzepine was blocked by ni fedipine (Ca2+ channel blocker), suggesting that pirenzepine (through release of endogenous ACh) provides an acute stimulus by enhancing Ca inflow. Hemicholine, a choline uptake blocker, reduced the stimulatory effect of pirenzepine on steroid secretion, confirming that stimulati on was of neural origin. Neither the non-selective muscarinic receptor antagonist atropine, the selective M-1-M-3 muscarinic receptor antago nist 4-DAMP, nor the selective M-2 muscarinic receptor antagonist meth octramine influenced aldosterone output. Receptor-binding studies reve aled the existence of M-3 receptors in capsule-glomerulosa homogenates . We conclude that pirenzepine acts on presynaptic M-1 autoreceptors t o increase spontaneous ACh release from varicose axon terminals that l ie in close proximity to the glomerulosa cells. In rum ACh may thus st imulate steroidogenesis acutely through Mg receptors. These results su pport the concept of a direct cholinergic influence on zona glomerulos a function in the rat.