The growth hormone secretagogue receptor (GHSR1a) and dopamine receptor 2 (DRD2) are co-expressed in spinal cord and brain where they are reported to interact to elicit effects on both defecation and appetite control. Ghrelin, the endogenous agonist of GHSR1a is absent from the central nervous system. Functional interaction between these receptors in spinal defecation centres and hypothalamus have previously been reported, including a proposed GHSR1a-DRD2 dimer in the hypothalamus. When co-expressed with GHSR1a, DRD2 activation increases neuronal excitability in the rat spinal cord and, in transfected cells, causes calcium mobilisation, both unexpected outcomes for DRD2 activation. In transfected cells, we used intracellular calcium mobilisation and inhibition of forskolin-mediated cAMP production as correlates of neuronal excitability and inhibition respectively to better understand the mechanism behind this interaction. We confirm GHSR1a dependent potentiation of DRD2-mediated calcium mobilisation and show cross-antagonism in this signalling response, but not of DRD2-mediated inhibition of cAMP production. We show coupling of GHSR1a to Gαq/11 and of DRD2 to Gαi/o, with activity of both Gαq/11 and Gαi/o being necessary for coupling of DRD2 activation to intracellular calcium mobilisation. Our confocal microscopy does not support a dimer. Our findings suggest that neuronal excitability reported following DRD2 activation in lumbosacral defecation centres is dependent on both DRD2 and GHSR1a as well as Gαq/11 and Gαi/o and could occur without direct interaction between the receptors. Our data is an important step towards understanding the mechanism through which these receptors interact, which may provide better therapeutic targeting for treatment of colorectal dysfunction.