Pages: > > NOT CUSTOM BLISTER END -->
A receptor which is capable of producing a biological response in the absence of a bound ligand is said to display "constitutive activity".  The constitutive activity of a receptor may be blocked by an inverse agonist . The anti-obesity drugs rimonabant and taranabant are inverse agonists at the cannabinoid CB1 receptor and though they produced significant weight loss, both were withdrawn owing to a high incidence of depression and anxiety, which are believed to relate to the inhibition of the constitutive activity of the cannabinoid receptor.
Voltage-gated dependent calcium channel , (VDCCs), are key in the depolarisation of neurons, and play a major role in promoting the release of neurotransmitters. When agonists bind to opioid receptors, G proteins activate and dissociate into their constituent Gα and Gβγ sub-units. The Gβγ sub-unit binds to the intracellular loop between the two trans-membrane helices of the VDCC. When the sub-unit binds to the voltage-dependent calcium channel, it produces a voltage-dependant block, which inhibits the channel, preventing the flow of calcium ions into the neuron. Embedded in the cell membrane is also the G protein-coupled inwardly-rectifying potassium channel . When a Gβγ or Gα(GTP) molecule binds to the C-terminus of the potassium channel, it becomes active, and potassium ions are pumped out of the neuron.  The activation of the potassium channel and subsequent deactivation of the calcium channel causes membrane hyperpolarization . This is when there is a change in the membrane’s potential, so that it becomes more negative. The reduction in calcium ions causes a reduction neurotransmitter release because calcium is essential for this event to occur.  This means that neurotransmitters such as glutamate and substance P cannot be released from the presynaptic terminal of the neurons. These neurotransmitters are vital in the transmission of pain, so opioid receptor activation reduces the release of these substances, thus creating a strong analgesic effect.