Control of transmitter release is not limited to modulation by the transmitter itself. Nerve terminals also carry regulatory receptors that respond to many other substances. Such heteroreceptors may be activated by substances released from other nerve terminals that synapse with the nerve ending. For example, some vagal fibers in the myocardium synapse on sympathetic noradrenergic nerve terminals and inhibit norepinephrine release. Alternatively, the ligands for these receptors may diffuse to the receptors from the blood or from nearby tissues. Some of the transmitters and receptors identified to date are listed in Table 6–4. Presynaptic
TABLE 6–3 Direct effects of autonomic nerve activity on some organ systems. Autonomic drug effects are similar but not identical (see text).
1Less important actions are shown in brackets. 2Specific receptor type: α, alpha; β, beta; M, muscarinic. 3Vascular smooth muscle in skeletal muscle has sympathetic cholinergic dilator fibers. 4The endothelium of most blood vessels releases EDRF (endothelium-derived relaxing factor), which causes marked vasodilation, in response to muscarinic stimuli. Parasympa thetic fibers innervate muscarinic receptors in vessels in the viscera and brain, and sympathetic cholinergic fibers innervate skeletal muscle blood vessels. The muscarinic receptors in the other vessels of the peripheral circulation are not innervated and respond only to circulating muscarinic agonists. 5Cerebral blood vessels dilate in response to M5 receptor activation. 6Probably through presynaptic inhibition of parasympathetic activity. 7The cholinergic innervation of the rectum and the genitourinary organs may be anatomically sympathetic; see Box: Sympathetic Sacral Outflow.
FIGURE 6–7 Autonomic and hormonal control of cardiovascular function. Note that two feedback loops are present: the autonomic nervous system loop and the hormonal loop. The sympathetic nervous system directly influences four major variables: peripheral vascular resistance, heart rate, force, and venous tone. It also directly modulates renin production (not shown). The parasympathetic nervous system directly influences heart rate. In addition to its role in stimulating aldosterone secretion, angiotensin II directly increases peripheral vascular resistance and facilitates sympathetic effects (not shown). The net feedback effect of each loop is to compensate for changes in arterial blood pressure. Thus, decreased blood pressure due to blood loss would evoke increased sympathetic outflow and renin release. Conversely, elevated pressure due to the administration of a vasoconstrictor drug would cause reduced sympathetic outflow, reduced renin release, and increased parasympathetic (vagal) outflow.
TABLE 6–4 Autoreceptor, heteroreceptor, and modulatory effects on nerve terminals in peripheral synapses.1 1A provisional list. The number of transmitters and locations will undoubtedly increase with additional research.
Late, slow EPSP
FIGURE 6–8 Excitatory and inhibitory postsynaptic potentials (EPSP and IPSP) in an autonomic ganglion cell. The postganglionic neuron shown at the left with a recording electrode might undergo the membrane potential changes shown schematically in the recording. The response begins with two EPSP responses to nicotinic (N) receptor activation, the first not reaching threshold. The second, suprathreshold, EPSP evokes an action potential, which is followed by an IPSP, probably evoked by M2 receptor activation (with possible participation from dopamine receptor activation). The IPSP is, in turn, followed by a slower, M1-dependent EPSP, and this is sometimes followed by a still slower peptide-induced excitatory postsynaptic potential.
regulation by a variety of endogenous chemicals probably occurs at all synapses.
C. Postsynaptic Regulation