Table 2.

Effects of metals on presynaptic signaling pathways (↑—activation/upregulation, ↓—inhibition/downregulation).

Target		Pathways
		PKC		Adenylate cyclase		Phosphodiesterase	CaM	IP3	Intracellular calcium
Al	Effect	↓	↑				↓		↑
	Conc	0–100 μM					0–1000 microM		0–1000 μM
	Ref	[2]	[23]				[2]		[2]
As	Effect								↑
	Conc								1 μM
	Ref								[24]
Cd	Effect				↓	↓			↑
	Conc				0.4, 0.9, 1.4 (i)  μM				0.1–1 mM
	Ref				[25], [25], [25]	[25]			[26]
Hg	Effect				↓	↓
	Conc				0.8, 0.5, 0.9 (i)  μM
	Ref				[25], [25], [25]	[25]
Ni	Effect	↓
	Conc	30 μM
	Ref	[27]
Pb	Effect			NC	↓	↓
	Conc			1500–10000 ppm	2.5, 8.6,1.9, 8.0 (i) μM
	Ref			[25]	[28], [25], [25], [25]	[25]
Pt	Effect							↑	↑
	Conc							1 nM–10 μM	1 nM–10 μM
	Ref							[29]	[29]
Zn	Effect				↓
	Conc				1-2 μM
	Ref				[30]

⁽ⁱ⁾The three different concentrations indicate actions in different areas of the brain—cerebrum, cerebellum, and brainstem.