Endogenous tone

The delta opioid knockout mice demonstrated behaviors consistent with anxiogenic- and depressivelike responses, suggesting that delta opioid receptors and endogenous tone of the delta opioid system may play a role in mood states and depression. 

There is now increasing evidence that cannabinoid receptors involved in the inhibition of neuroeffector transmission are subject to an endogenous tone (Table 5). A typical example is the presynaptic CB, receptors on GABAergic neurons synaps-ing with the pyramidal neurons in the rat hippocampus (Wilson and Nicoll 2001). Depolarisation of the latter neurons causes an increase in formation of endo-... 

Table 5. Endogenous tone at CBi receptors inhibiting neuroeffector transmission (continued on next page)... 

Neurotransmitter Species Tissue Method Identification of endogenous tone Reference(s)... 

The facilitatory effect of inverse agonists on transmitter release was mimicked in some paradigms by the disruption of CBi receptors, i.e. transmitter release was higher in tissues from CBi receptor-deficient mice when compared to wildtype animals (Table 5). This experimental approach does not allow one to reach a conclusion as to whether the endogenous tone is related to accumulation of endocannabinoids or constitutively active CBi receptors yet it is remarkable that blockade of, or inverse agonism at, CBi receptors during the course of the experiment and complete lack of CBi receptors have the same consequence. 

Schlicker E, Liedtke S, Flau K, Kathmann M (2002) Further evidence that fhe cannabinoid receptor inhibiting noradrenaline release in the guinea-pig brain belongs to the CBi subtype and is subject to an endogenous tone. Pharmacologist 44(Suppl 1) A112... 

In just one decade, endocannabinoids have been shown to play manifold roles, both in the CNS and in the periphery. In particular, it is now widely accepted that the biological activity of AEA and 2-AG is largely dependent on a metabolic control , that modulates the effects of these substances by modulating their in vivo concentration (or endogenous tone) (Cravatt and Lichtman, 2002). 

Metitepine enhances release endogenous tone at receptor [114]... 

Alpha antagonists are administered primarily to reduce peripheral vascular tone by blocking the alpha-1 receptors located on vascular smooth muscle. When stimulated by endogenous catecholamines (norepinephrine, epinephrine), the alpha-1 receptor initiates vasoconstriction. 

The renin-angiotensin system involves several endogenous components that help regulate vascular tone in various organs and tissues.25,84,109 In systemic circulation, the renin-angiotensin system acts by a sequence of events summarized in Figure 21-2. Renin is an enzyme produced primarily in the kidneys. When blood pressure falls, renin is released from the kidneys into the systemic circulation. Angiotensinogen is a peptide that is produced by the liver and circulates... 

A synthetic form of the endogenous peptide brain natriuretic peptide (BNP) has recently been approved for use in acute cardiac failure as nesiritide. This recombinant product increases cGMP in smooth muscle cells and effectively reduces venous and arteriolar tone in experimental preparations. It also causes diuresis. The peptide has a short half-life of about 18 minutes and is administered as a bolus intravenous dose followed by continuous infusion. Excessive hypotension is the most common adverse effect. Measurement of endogenous BNP has been proposed as a diagnostic test because plasma concentrations rise in most patients with heart failure. 

Receptor Type Endogenous Agonist G protein, Second Messenger Smooth Muscle Tone Result of Receptor Knockout... 

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