The influence of Prostaglandin E2 on bradykinin induced depolarization, generation and conduction of action potentials in the isolated vagus nerve

Dr Charles Murimi Mugera MSc Pharmacology 
Prostanoids, in particular prostaglandin I (PGI) and prostaglandin E (PGE), are 
2222
generated in response to tissue injury or inflammation (Bombardieri et al., 1981). 
Prostanoids, unlike bradykinin, do not produce pain but potentiate the response to pain. 
PGE has a potentiating effect on the sensitivity of vagal C fiber activity in response to 
2
chemical or mechanical stimulation (Lee & Morton, 1995; Ho et al., 2000). Analgesic 
effects of non-steroidal anti-inflammatory drugs (NSAIDs) are attributed predominantly 
to inhibition of prostaglandin synthesis. Therefore, this implies that there is huge scope 
for development of far more potent analgesics by furthering our understanding of the 
interaction between the mediators that produce pain, such as bradykinin, and the 
mediators that potentiate the pain such as PGE. 
2
 Receptors mediating the actions of prostanoidshave been identified and cloned from 
human tissues (Pierce et al., 1995; Ushikubi et al., 1995) . They are G protein-coupled
rhodopsin-type receptor with seven transmembrane domains. There are eight types of 
prostanoid receptors TP, IP, EP, EP, EP, EP FP, and DP. TP and IP are coupled to the 
1234
G alpha s and G alpha q respectively. EP1 acts by an unknown mechanism to cause an 
2+
increase in Ca, EP2 and EP4 are coupled to G alpha s and cause increased activity of 
adenylate cyclase. EP 3 is predominantly coupled to G alpha s or G alpha I (Narumiya et 
al., 1999). The different types of prostanoids receptors and their second messenger 
systems have been summarised on Table 1.1. It has been suggested that prostanoids 
contribute to the development of pain mainly through EP1 or IP receptors (Minami et al., 
2001; Stock et al., 2001; Moriyama et al., 2005). 
4 
The Wolfson Centre for Age-Related Diseases