How can nitric oxide signal without vesicles, receptors on the surface or a synapse? · Grey Matter

Nitric oxide is a small gas, so it is made at the moment it is needed and leaves the cell by diffusing straight through membranes.

How can nitric oxide signal without vesicles, receptors on the surface or a synapse?

Nitric oxide is a small gas, so it is made at the moment it is needed and leaves the cell by diffusing straight through membranes. Its synthesising enzyme in neurons, nNOS, is activated by calcium and calmodulin and is often anchored next to NMDA receptors, so glutamate signalling that lets calcium in also makes nitric oxide. It spreads to nearby cells in all directions, including back to the presynaptic terminal, and acts on soluble guanylyl cyclase inside them, which makes the second messenger cyclic GMP. The signal cannot be aimed or stored, so it reports the level of local activity to everything within reach until it decays.