Functional analysis of guinea pig β1-adrenoceptor.

Although similarity of pharmacological responses to certain stimuli between guinea pigs and humans has been reported, this has been poorly defined by a molecular biological approach. In this study, we cloned the gene of guinea pig ?1-adrenoceptor (ADRB1). The deduced amino acid sequence of guinea pig ADRB1 (467-aa) showed 91% and 92% identity with the human and rat ADRB1 sequences, respectively. Using HEK293T cells expressing guinea pig, human and rat ADRB1s independently, we elucidated the functional characteristics of each ADRB1. The ligand-binding profiles and the concentration-response relationships for isoprenaline-induced cyclic adenosine monophosphate (cAMP) production were similar among the three ADRB1s. Isoprenaline also induced phosphorylation of extracellular-signal related kinases (ERK) through ADRB1s in a concentration-dependent manner. The minimum effective concentration of isoprenaline for phosphorylation of ERK, through guinea pig ADRB1 was the same as through human ADRB1, but markedly lower than that of through rat ADRB1. ERK phosphorylation through guinea pig ADRB1 was sensitive to pertussis toxin, a dominant-negative ras and PD98059, indicating that a G(i)-mediated pathway is involved in the ADRB1/ERK signaling loop. These results suggest that the G(i)-coupling efficacy of guinea pig and human ADRB1s may be higher than that of rat ADRB1.