TABLE 3.

SIGNAL TRANSDUCTION PATHWAYS FOR CATECHOLAMINE RECEPTORS

Receptor

     G-Protein^a

Effectors^b

Adrenergic

b₁, b₂

        Gs

Adenylyl cyclase ( ­ )

a_1A^c

        Gi/o

Ca²⁺ ( ­ )

a_1B^c

        Gq

Inositol triphosphate ( ­ )

a_1C^c

        Gq

Inositol triphosphate ( ­ )

a_1D^c

        Gq

Inositol triphosphate ( ­ )

a_2A/D^d

        Gi

Adenylyl cyclase ( ¯ ), K⁺ ( ­ ), Ca²⁺ ( ¯ )

a_2B

        Gi_2,3^e

Adenylyl cyclase ( ¯ )

a_2C

        Go^e

Adenylyl cyclase ( ¯ )

Dopaminergic

D₁, D₅

        Gs

Adenylyl cyclase ( ­ )

D₂, D₃, D₄

        Gi/o

Adenylyl cyclase ( ¯ ), K⁺ ( ­ ), Ca²⁺ ( ¯ )

a

G-protein utilized by each receptor could vary depending on the brain region and effector systems present.  Pertussis toxin has been useful in determining the type of G-protein utilized by different receptors:  Gq and Gz are insensitive, while Gi and Go are inactivated by toxin treatment.  Gz is not included in the Table:  it is reported to mediate inhibition of adenylyl cyclase in cultured cells, but a role in mediating catecholamine receptor regulation of adenylyl cyclase has not been demonstrated.

b

The Table lists the primary action(s) mediated by G-protein a subunits. Different, and sometimes opposing, effects may be produced by G-protein bg subunits.

c

There are several cases of a-adrenergic stimulation of cGMP levels, presumably mediated via Ca²⁺ stimulation of nitric oxide synthase and subsequent nitric oxide stimulation of guanylyl cyclase.

d

a_2A and a_2D receptors appear to be human and rat homologues, respectively, with slightly different pharmacological profiles.

e

a_2B and a_2C prefer these G protein subtypes when expressed in cultured cells, but may utilize other G-protein subtypes in vivo.