## 10 Conclusions  
cAMP-dependent signaling pathways in the Apicomplexa and kinetoplastids are unique since canonical heterotrimeric G-proteins and GPCRs are absent in both groups. However, cAMP is essential for the stage conversion in the complex life cycles of apicomplexan parasites and kinetoplastids. Instead, membrane bound adenylyl cyclases and small GTPases may partly substitute the heterotrimeric G-proteins in signal transduction. In the Apicomplexa, mostly in _Plasmodium_, Rab families which belong to the Ras superfamily, are mainly involved in the regulation of vesicular transport and endocytic pathways during invasion of the host cell. A novel function, i.e., developmental regulation occurs in case of a not further characterized GTPase in _Cryptosporidium_. Small GTPases have not been described in _Toxoplasma gondii_, but rhoptry associated pseudokineses interact with immunity-related host GTPases Gbp2 and Irga6 during _Toxoplasma gondii_ infection. However, an inhibitor has not been identified against the characterized GTPases in the Apicomplexa. In contrast, in Kinetoplastids plenty of small GTPases of the Ras family have been identified with particular functions, e.g., in endocytosis to evade the host innate immune response or flagellar motility. Host heterotrimeric G-proteins and GPCRs are also involved in the parasite-host interaction and required for parasitic invasion. Thus additional chemotherapeutic approaches targeting canonical pathways of the human host are necessary for the eradication of the parasite. This has already been successfully shown by inhibition of the human \(\beta\)-adrenergic receptor with propranolol in _Plasmodium_ infected human erythrocytes [23]. Secondary effectors like adenylylcyclases, cAMP-dependent kinases and phosphodiesterase are present in the Apicomplexa and kinetoplastids. The most attractive target in the Apicomplexa is the small GTPase Rap-1 which is activated by cAMP through the guanine nucleotide exchange factor independently of protein kinase A. Currently, no inhibitor against Rap-1 has been identified although imidazopyrimidines inhibit calcium-dependent protein kinase1 (CDPK1) which is activated by Rap-GTP through Ca ion release in many stages of the _Plasmodium_ life cycle [119]. Plenty of the secondary effectors have not only been structurally characterized but also investigated with respect to pathogenicity. Hence, the uniqueness of these proteins may be exploited in drug discovery for antiparasitic chemotherapy. Targeting of plasmodial ACG kinases has just begun. Adenosine analogue-oligoarginine conjugates inhibit a cGMP-dependent protein kinase which is a representative member of the _Plasmodium_ kinome [119]. In _Toxoplasma gondii_ a cAMP-dependent kinase was identified [120; 121] being responsible for tachyozoite growth. The ATP-competitive inhibitor did not only have a strong effect on the protein but also inhibited tachyozoite growth. At present, there is a lack of reports on cAMP-dependent effector proteins in _Cryptosporidium_. Adenylate cyclases, phosphodiesterase and cAMP- dependent kinases with significant differences to their human orthologues have been characterized in _Trypanosoma_ and _Leishmania_. ACs are highly abundant in trypanosomes with one single transmembrane domain and dimeric function in contrast to their human counterpart. They are proposed to be mainly involved in cytokinesis and evasion of the host immune response. In particular, it remains a mystery why _T. brucei_ has evolved such a high number of genome-encoded ACs [122]. To further study the link between immune invasion and resolution of plenty of incoming signals could spark an interesting process in drug development. _Leishmania major_ has a soluble heme-containing AC which can be activated in response to oxygen [123]. To date, no pharmacological inhibitor against this AC in Leishmania species and the ACs in trypanosomes has been identified. Phoshodiesterases (PDEs) have found to be essential to cell survival and virulence in the kinetoplastids.