Retrograde neuronal tracing in combination with double-labelling immun
ofluorescence was applied to distinguish the chemical coding of guinea
-pig primary sensory neurons projecting to the adrenal medulla and cor
tex. Seven subpopulations of retrogradely traced neurons were identifi
ed in thoracic spinal ganglia T1-L1. Five subpopulations contained imm
unolabelling either for calcitonin gene-related peptide (CGRP) alone (
I), or for CGRP, together with substance P (II), substance P/dynorphin
(III), substance P/cholecystokinin (IV), and substance P/nitric oxide
synthase (V), respectively. Two additional subpopulations of retrogra
dely traced neurons were distinct from these groups: neurofilament-imm
unoreactive neurons (VI), and cell bodies that were nonreactive to ei
ther of the antisera applied (VII). Nerve fibres in the adrenal medull
a and cortex were equipped with the mediator combinations I, II, IV an
d VI. An additional meshwork of fibres solely labelled for nitric oxid
e synthase was visible in the medulla. Medullary as well as cortical f
ibres along endocrine tissue apparently lacked the chemical code V, wh
ile in the external cortex some fibres exhibited code III. Some intram
edullary neuronal cell bodies revealed immunostaining for nitric oxide
synthase, CGRP or substance P, providing an additional intrinsic adre
nal innervation. Perikarya, immunolabelled for nitric oxide synthase,
however, were too few to match with the large number of intramedullary
nitric oxide synthase-immunoreactive fibres. A non-sensory participat
ion is also supposed for the particularly dense intramedullary network
of solely neurofilament-immunoreactive nerve fibres. The findings giv
e evidence for a differential sensory innervation of the guinea-pig ad
renal cortex and medulla. Specific sensory neuron subpopulations sugge
st that nervous control of adrenal functions is more complex than hith
erto believed.