Explain the action of : Caffeine, Viagra and Pertussis toxin.

CAFFEINE:

It is the most widely consumed central nervous system stimulant. Mobilization of intracellular calcium and inhibition of specific phosphodiesterase only occur at high non-physiological concentrations of caffeine. Caffeine increases energy metabolism throughout the brain but decreases at the same time cerebral blood flow, including a brain hypo perfusion.  Caffeine activates adrenaline neurons  and seems to affect the local release of dopamine. It exerts obvious effects on anxiety and sleep which vary according to individual sensitivity. The CNS does not seem to develop a great tolerance to the effects of caffeine although dependence and withdrawal symptoms are reported. Caffeine increases the release of acid in the stomach. Sometimes leading to an upset stomach or heart burn. It has been associated with increased urine volume and frequently causing the blood to lose water and electrolytes like Na+/K+.

VIAGRA:

It belongs to the class of PDE5 inhibitor drugs which inhibit or block the chemicals known as Phosphodiesterase inhibitor drugs. The sexual stimulation releases nitric oxide in the corpus cavernous, the two parallel channels situated at the sides along the length of the penis. The release of NO activates the enzyme guanylyl cyclase which results in the increased levels of cGMP responsible for penile erection.

Viagra works by inhibiting the chemical PD type 5 which is responsible for the erections turning flaccid. This prolongs the effect of the muscle relaxation in the corpus cavernous area of the penis allowing the blood to flow into the spongy tissues of the penis causing an erection. It does not have any direct relevant effect on the corpus cavernous area in the human penis but enhances the effect of NO by inhibiting PDE5 which is responsible for degradation of cGMP in the corpus cavernous. When sexual stimulation causes local release of NO the inhibition of PDE5 by Viagra causes increase level of cGMP in corpus cavernous, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernous resulting in the required erections of the penis.

 PERTUSSIS TOXIN:

It is a secreted protein exotoxin and an important virulence factor produced exclusively by beta-pertussis. It is a complex multisubunit toxin with an AB5 configuration (one active subunit plus five binding subunits). It is a pentameric ring composed of subunits S2, S3 two S4, S5 which bind to various glycoconjugate molecules in the surface of target cell.

• S2 and S3 each contain two different carbohydrates binding domains, which most likely accounts for the capacity of PT to bind to and intoxicate virtually any mammalian cell.
• The enzymatic activity of PT residues in the A-subunit also known as S1.
• S1 hydrolyzes cellular NAD and transfers the released ADP-ribose to a specific cysteine residue near the C-terminus of the alpha-subunit of heterotrimeric G-proteins of the Gi family in mammalian cells.
• This modification results in inhibition of Gi protein-coupled signaling pathways, causing a variety of downstream effects.
• Pertussis toxins also binds to glycosylated molecules on the surface of mammalian cells and enters cells by endocytosis.