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Gamma-aminobutyric acid (GABA) and its receptors are found in a wide range of peripheral tissues, including parts of the peripheral nervous system, endocrines, and non-neural tissues such as smooth muscle and the female reproductive system. In all these, both GABAA- and GABAB-receptor types are found, with good evidence for a physiological role in the gut, pancreatic islets and the urinary bladder. In some tissues, the pharmacology of GABA-induced actions is quite atypical and should be further explored with the newer ligands and modulators for GABAA- and GABAB-receptors.

The distribution of calcitonin gene-related peptide immunoreactivity in the cardiovascular system of the rat was investigated by radioimmunoassay and immunocytochemistry. The nature of the immunoreactivity was studied by gel permeation and high performance liquid chromatography. Immunocytochemistry demonstrated the existence of calcitonin gene-related peptide-containing nerve fibres throughout the cardiovascular system. These were present in all regions of the heart, particularly in association with the coronary arteries, within the papillary muscles and within the sinoatrial and atrioventricular nodes. Calcitonin gene-related peptide-containing fibres were found mainly in the adventitia of the arteries and veins. Calcitonin gene-related peptide concentrations were high in major arteries and veins but comparatively low in the heart, aortic arch and thoracic aorta. Chromatography showed that approximately 70% of the total immunoreactivity was identical to synthetic calcitonin gene-related peptide. Calcitonin gene-related peptide concentrations in the blood vessels of rats treated neonatally with capsaicin were not found to be significantly different from those in control animals although capsaicin caused significant reductions of calcitonin gene-related peptide levels in certain other tissues. The results of this study suggest that calcitonin gene-related peptide-containing fibres are likely to be of importance in the innervation of vascular tissues and raise the possibility that these fibres are different in character from calcitonin gene-related peptide-containing fibres found in other tissues.

1. Autoradiographic techniques have been used to examine the location of beta-adrenoceptors in the heart and beta-adrenoceptors, substance P receptors and muscarinic cholinoceptors in blood vessels. 2. Both beta 1-adrenoceptors and beta 2-adrenoceptors were present in guinea-pig and human heart, on the myocardium and associated with the cardiac nerves and blood vessels. 3. Nerves on the vasculature and vascular smooth muscle contained beta-adrenoceptors and muscarinic cholinoceptors. 4. Receptors for substance P and beta-adrenoceptors, but not muscarinic cholinoceptors were present on endothelial cells.

PHI (peptide with histidine and isoleucine) and NPY (neuropeptide with tyrosine) are recently discovered regulatory peptides. There are close sequence similarities between PHI and both growth hormone releasing factor (GRF) and vasoactive intestinal polypeptide (VIP) and between NPY and pancreatic polypeptide. Using immunocytochemistry and radioimmunoassay we have revealed the broad distributions of PHI and NPY in neurons of the central nervous system and the majority of peripheral tissues. Tissues which are particularly well provided with these peptides include gut, pancreas, respiratory tract, skin and the genitourinary and cardiovascular systems. In most peripheral tissues, PHI-containing ganglion cells occur locally. NPY-containing fibres originate in part from cell bodies outside the tissues, in the sympathetic nervous system. Comparative studies indicate that PHI and VIP are co-stored in the same neurone and are identically distributed, thus suggesting the existence of a common precursor and subsequent gene duplication. The possible co-existence of catecholamines and NPY, suggested by the consistent finding of very similar distributions of the two substances, was investigated using antibodies to converting enzymes involved in catecholamine synthesis (tyrosine-hydroxylase and dopamine-beta-hydroxylase). The two enzymes and NPY were found together in at least part of the same neuronal system.

The equation describing kinetics of interaction between bradykinin and cardiovascular receptors resembles the equations describing depressive adrenergic and some cholinergic reactions in dogs, rabbits and white rats. In this study of bradykinin receptor state, in order to describe quantitatively hypotensive action of different bradykinin doses on interaction of this peptide with receptors, bradykinin had to be injected intraaortally. The data obtained revealed that the greatest efficiency of kininergic reaction occurred in dogs whereas the least--in white rats.

Isolation of the DNA sequence encoding neuropeptide Y (NPY) has suggested the presence of a precursor peptide consisting of 97 aminoacids. Three peptide products have been predicted from this precursor; an N terminal signal peptide, neuropeptide Y and a C terminal 30 amino acid flanking peptide. This study has demonstrated by a novel radioimmunoassay that this C-flanking peptide for NPY occurs naturally in tissues. The peptide is present in abundance throughout the central nervous system and qualitatively in both the brain and peripheral structures, it has the same distribution as NPY. Chromatographic analysis demonstrated that the measured CPON-immunoreactivity elutes in the position of the peptide synthesised according to the predicted sequence.

alpha-Adrenoceptors may be subdivided based on their anatomical distribution within the synapse. Presynaptic alpha-adrenoceptors are generally of the alpha 2-subtype and modulate neurotransmitter liberation via a negative feedback mechanism. Postsynaptic alpha-adrenoceptors are usually of the alpha 1-subtype and mediate the response of the effector organ. Although this "anatomical" subclassification is generally applicable, many exceptions exist. A more useful classification of alpha-adrenoceptor subtypes is based on a pharmacological characterization in which selective agonists and antagonists are used. Peripheral alpha-adrenoceptors are critical in the regulation of the cardiovascular system. Postsynaptic alpha-adrenoceptors in arteries and veins represent a mixed population of alpha 1/alpha 2-adrenoceptors, with both subtypes mediating vasoconstriction. In the peripheral arterial circulation, postsynaptic vascular alpha 1-adrenoceptors are found in the adrenergic neuroeffector junction, whereas postsynaptic vascular alpha 2-adrenoceptors are located extrajunctionally. In the venous circulation, it appears that alpha 2-adrenoceptors may be predominantly junctional, whereas alpha 1-adrenoceptors may be predominantly extrajunctional. It has been proposed that junctional alpha-adrenoceptors will respond predominantly to norepinephrine liberated from sympathetic neurons, whereas extrajunctional alpha-adrenoceptors likely respond to circulating catecholamines. The functional role of extrajunctional alpha-adrenoceptors may be more important in disease states such as hypertension and congestive heart failure where circulating levels of catecholamines may be high and contribute to the maintenance of elevated vascular resistance. alpha 2-Adrenoceptors are also associated with the intima and may play a role in the release of an endogenous relaxing factor from the endothelium.(ABSTRACT TRUNCATED AT 250 WORDS)