▁Both ▁trans du ce ▁the ▁h orm one ▁binding ▁to ▁int rac ell ular ▁signal ing ▁via ▁second ▁mess enger ▁cas c ades . ▁ ▁The ▁AM 2 ▁re ceptor ▁has ▁a ▁low ▁aff inity ▁for ▁CG R P , ▁but ▁this ▁is ▁of ▁no ▁phys i ological ▁relev ance . ▁ ▁Un like ▁the ▁classical ▁one ▁lig and - one ▁re ceptor ▁notion ▁of ▁re ceptor ▁sign alling , ▁the ▁interaction ▁of ▁both ▁C AL C RL ▁and ▁RA MP ▁at ▁the ▁memb rane ▁is ▁ ▁required ▁for ▁AM ▁to ▁medi ate ▁its ▁action : ▁neither ▁can ▁bind ▁the ▁h orm one ▁( and ▁therefore ▁trans du ce ▁a ▁signal ) ▁alone . ▁Stim ulation ▁by ▁AM ▁of ▁its ▁re ceptor ▁increases ▁production ▁of ▁both ▁cy clic ▁A MP ▁( c AMP ) ▁and ▁nit ric ▁ox ide . ▁ ▁Before ▁the ▁discovery ▁of ▁the ▁RA MP s ▁and ▁the ▁identification ▁of ▁heter omer ic ▁re cept ors ▁for ▁the ▁cal cit on in ▁family ▁of ▁pe pt ides , ▁a ▁single ▁G ▁Prote in ▁couple d ▁Ad ren omed ull in ▁re ceptor ▁was ▁identified , ▁but ▁more ▁recent ▁reports ▁have ▁cast ▁doub ts ▁as ▁to ▁its ▁importance ▁in ▁the ▁major ▁effects ▁of ▁ad ren omed ull in . ▁In ▁more ▁recent ▁research , ▁the ▁roles ▁of ▁the ▁AM 1 ▁and ▁AM 2 ▁re cept ors ▁have ▁been ▁clar ified ▁through ▁studies ▁in ▁gen et ically ▁manip ulated ▁m ice . ▁ ▁The ▁ad ren omed ull in ▁knock out ▁is