Alpha receptors
It later became possible to separate these main groups of receptors further, into a1 and a2 based on the selectivity of the antagonists prazosin, the antihypertensive agent that blocks a1 receptors, and yohimbine, which is an antagonist of a2 receptors. At one time it was thought that a1 receptors were postsynaptic and the a2 type were presynaptic and concerned with the inhibitory control of noradrenaline release. Indeed, novel antidepressants like mianserin, and more recently the highly selective a2 receptor antagonist idazoxan, or yohimbine, were thought to act by stimulating the relase of noradrenaline from central noradrenergic synapses. It is now established, however, that the a2 receptors also occur postsynaptically, and that their stimulation by such specific agonists as clonidine leads to a reduction in the activity of the vasomotor centre, thereby leading to a decrease in blood pressure. Conversely, the a2 antagonist yohimbine enhances noradrenaline release . The a1 receptors are excitatory in their action, while the a2 receptors are inhibitory, these activities being related to the different types of second messengers or ion channels to which they are linked. Thus, a2 receptors hyperpolarize presynaptic membranes by opening potassium ion channels, and thereby reduce noradrenaline release. Conversely, stimulation of a1 receptors increases intracellular calcium via the phosphatidyl inositol cycle which causes the release of calcium from its intracellular stores; protein kinase C activity is increased as a result of the free calcium, which then brings about further changes in the membrane activity. Both types of receptor occur in the brain as well as in vascular and intestinal smooth muscle: a1 receptors are found in the heart whereas a2 receptors occur on the platelet membrane (stimulation induces aggregation) and nerve terminals (stimulation inhibits release of the transmitter). It is now recognized that there are several subtypes of a1 and a2 receptors, but their precise function is unclear.
It later became possible to separate these main groups of receptors further, into a1 and a2 based on the selectivity of the antagonists prazosin, the antihypertensive agent that blocks a1 receptors, and yohimbine, which is an antagonist of a2 receptors. At one time it was thought that a1 receptors were postsynaptic and the a2 type were presynaptic and concerned with the inhibitory control of noradrenaline release. Indeed, novel antidepressants like mianserin, and more recently the highly selective a2 receptor antagonist idazoxan, or yohimbine, were thought to act by stimulating the relase of noradrenaline from central noradrenergic synapses. It is now established, however, that the a2 receptors also occur postsynaptically, and that their stimulation by such specific agonists as clonidine leads to a reduction in the activity of the vasomotor centre, thereby leading to a decrease in blood pressure. Conversely, the a2 antagonist yohimbine enhances noradrenaline release . The a1 receptors are excitatory in their action, while the a2 receptors are inhibitory, these activities being related to the different types of second messengers or ion channels to which they are linked. Thus, a2 receptors hyperpolarize presynaptic membranes by opening potassium ion channels, and thereby reduce noradrenaline release. Conversely, stimulation of a1 receptors increases intracellular calcium via the phosphatidyl inositol cycle which causes the release of calcium from its intracellular stores; protein kinase C activity is increased as a result of the free calcium, which then brings about further changes in the membrane activity. Both types of receptor occur in the brain as well as in vascular and intestinal smooth muscle: a1 receptors are found in the heart whereas a2 receptors occur on the platelet membrane (stimulation induces aggregation) and nerve terminals (stimulation inhibits release of the transmitter). It is now recognized that there are several subtypes of a1 and a2 receptors, but their precise function is unclear.
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