Regulation of cyclic GMP levels in nerve tissue

In rat superior cervical ganglia the regulation of cyclic GMP (cGMP) formation does not involve muscarinic or adrenergic transmitters or receptors. Marked increases in cGMP content during preganglionic axonal stimulation by electric currents, elevated K+, or drugs that cause transmitter release are unaffected by muscarinic and adrenergic receptor blockade. However, the cGMP response does require Ca2+ and intact preganglionic axonal terminals. Two possibilities exist: either cGMP accumulates in the preganglionic nerves or a noncholinergic, nonadrenergic transmitter activates guanylate cyclase in postsynaptic structures. Sodium azide and nitroprusside cause cGMP accumulation in denervated ganglia, which indicates that postsynaptic structures are capable of forming cGMP. In pineal glands elevated [K+]o releases [3H]norepinephrine and causes cGMP accumulation, which suggests a relationship between the two responses and the possibility that cGMP accumulation is involved in autoinhibition of transmitter release. The finding that phentolamine, alpha-adrenergic receptor antagonists, prevent the cGMP response to K+ is compatible with this review. However, clonidine, an alpha-receptor agonist, depresses norepinephrine release but has no effect on pineal gland cGMP. Conversely, large increases in pineal gland cGMP produced by nitroprusside do not affect K+-evoked norepinephrine release. For these reasons it is not possible to relate cGMP to the auto-inhibition of [3H]norepinephrine release that is mediated by prejunctional alpha-adrenergic receptors.